Search

Background: A rhesus macaque with the fourth highest plasma cholesterol (CH) levels of 501 breeding macaques was identified 22 years ago. Seven offspring with gene mutations causing hypercholesterolemia were obtained. Methods: Activity of low‐density lipoprotein receptor (LDLR), plasma CH levels and mRNA expression levels of LDLR were measured after administration of 0.1% (0.27 mg/kcal) or 0.3% CH. Results: Activity of p. (Cys82Tyr) of LDLR was 71% and 42% in the heterozygotes and a homozygote, respectively. The mRNA expression level of LDLR in the p. (Val241Ile) of membrane‐bound transcription factor protease, site 2 (MBTPS2, S2P protein) was 0.83 times lower than normal levels. LDLR mRNA levels were increased for up to 4 weeks by administration of 0.3% CH before suddenly decreasing to 80% of the baseline levels after 6 weeks. Conclusion: Oligogenic mutations of p. (Cys82Tyr) in LDLR and p. (Val241Ile) in MBTPS2 (S2P) caused hypercholesterolemia exceeding cardiovascular risk levels under a 0.1% CH diet. [ABSTRACT FROM AUTHOR]

The aim of the work was to study the pathogenicity of newly emerging variants of SARS-CoV-2 on the model of the Syrian golden hamster.Materials and methods. We used the strains of SARS-CoV-2 virus related to the VOC circulating in the territory of the Russian Federation. The experiments were carried out on outbreed Syrian hamsters obtained from the nursery of the SSC VB “Vector”. The infectious titer of coronavirus in tissue samples collected from infected laboratory animals was determined on a Vero E6 cell culture. The Ct in RT-PCR was considered an additional parameter for monitoring the viral load in the samples. The severity of lung tissue damage in Syrian hamsters with COVID-19 was assessed by histological preparations.Results and discussion. 50 % infecting doses in case of the intranasal infection have been determined, histological analysis of lung tissues performed. The pathogenicity of various variants of the SARS-CoV-2 virus for the Syrian hamster has been evaluated, differences in infecting doses and pathological changes in the lungs have been revealed. SARS-CoV-2 viruses belonging to Beta genetic variant have the highest virulence, while Alpha variant has the lowest one when comparing the studied strains by the ID50 value. The Delta and Omicron variants have a matched ability to cause specific damage to the tissues of the respiratory tract, while being inferior only to the Beta variant. It has been demonstrated that Syrian hamsters are an adequate model for assessing the pathogenicity of the SARS-CoV-2 virus variants of concern. Variants of SARS-CoV-2 virus during intranasal infection has shown different degree of pathogenicity in the Syrian hamster model.

Diabetic foot ulcers cause great suffering and are costly for the healthcare system. Normal wound healing involves hemostasis, inflammation, proliferation, and remodeling. However, the negative factors associated with diabetes, such as bacterial biofilms, persistent inflammation, impaired angiogenesis, inhibited cell proliferation, and pathological scarring, greatly interfere with the smooth progress of the entire healing process. It is this impaired wound healing that leads to diabetic foot ulcers and even amputations. Therefore, drug screening is challenging due to the complexity of damaged healing mechanisms. The establishment of a scientific and reasonable animal experimental model contributes significantly to the in-depth research of diabetic wound pathology, prevention, diagnosis, and treatment. In addition to the low cost and transparency of the embryo (for imaging transgene applications), zebrafish have a discrete wound healing process for the separate study of each stage, resulting in their potential as the ideal model animal for diabetic wound healing in the future. In this review, we examine the reasons behind the delayed healing of diabetic wounds, systematically review various studies using zebrafish as a diabetic wound model by different induction methods, as well as summarize the challenges and improvement strategies which provide references for establishing a more reasonable diabetic wound zebrafish model. [ABSTRACT FROM AUTHOR]

The aim of the research was to assess the susceptibility of mice of different lines to newly emerging variants of SARS-CoV-2.Materials and methods. The SARS-CoV-2 virus strains belonging to variants of concern (VOC) circulating in the territory of the Russian Federation were used in the study. Experiments involved three inbred mouse lines (BALB/c, CBA and C57Bl/6z) and CD1 outbred mice taken from the nursery of the SSC VB “Vector” of the Rospotrebnadzor. The infectious titer of coronavirus in tissue samples obtained from the laboratory animals was determined on a Vero E6 cell culture. The (Ct) threshold value in RT-PCR was considered an additional parameter for monitoring the viral load in the samples. The severity of lung tissue damage was assessed using histological preparations.Results and discussion. The susceptibility of various mouse lines to the genetic variant Beta of the SARS-CoV-2 virus has been investigated. During intranasal infection of the inbred and outbred mice with strains of VOC at a dose of 2·103 TCID50, the virus replicated in the lungs with maximum concentrations 72 hours after infection. The pathogenicity of genetic variants of the SARS-CoV-2 virus for BALB/c mice has been assessed, a 50 % infectious dose for intranasal infection (ID50) determined. Histological analysis showed COVID-19-specific lung tissue lesions in infected animals. Our study proves that BALB/c mice can be used as a model animal in screening studies when evaluating the effectiveness of therapeutic, vaccine preparations and studying the pathogenesis caused by VOC of the SARS-CoV-2 virus: Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Omicron (B.1.1.529) and the like.

Craniofacial anomalies encompassing the orofacial cleft are associated with > 30% of systemic congenital malformations. Baraitser-Winter Cerebrofrontofacial syndrome (BWCFF) is a rare genetic disorder attributed to variants in the actin beta (ACTB) or actin gamma genes that are correlated with a range of craniofacial abnormalities, including cleft lip and/or palate. The underlying pathological mechanism of BWCFF remains elusive, and it is necessary to investigate the etiology of orofacial clefts in patients with BWCFF. In this study, we identified a missense variant (c.1043C > T: p.S348L) in the ACTB gene of a patient with BWCFF and concomitant cleft lip and palate. Furthermore, we performed functional assessments of this variant using various disease models such as the MDCK cell line and Xenopus laevis. These models revealed a compromised capacity of mutated ACTB to localize to the epithelial junction, consequently affecting the behavior of epithelial cells. Additionally, we discovered that the mutated ACTB exhibited an impaired ability to bind PROFILIN1, a critical factor in actin polymerization. This defective ability may contribute to the molecular etiology of aberrant epithelial cell adhesion and migration, resulting in orofacial cleft formation in BWCFF., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Fungi play a fundamental role in the intestinal ecosystem and health, but our knowledge of fungal composition and distribution in the whole gastrointestinal tract (GIT) is very limited. The physiological similarity between humans and pigs in terms of digestive and associated metabolic processes places, the pig in a superior position over other non-primate models. Here, we aimed to characterize the diversity and composition of fungi in the GIT of pigs. Using high-throughput sequencing, we evaluated the fungal community in different locations of GIT of 11 pigs with 128.41 ± 1.25 kg body weight acquired successively. Among them, five pigs are sacrificed in April 2019 (Batch 1) and the other six are sacrificed in January 2020 (Batch 2). All subjects with similar genetic backgrounds, housing, management, and diet. Finally, no significant difference is found in the α-diversity (Richness) of the fungal community among all intestinal segments. Basidiomycota and Ascomycota are the two predominant fungal phyla, but Batch 1 harbored a notably high abundance of Basidiomycota and Batch 2 harbored a high abundance of Ascomycota. Moreover, the two batches harbored completely different fungal compositions and core fungal genera. FUNGuild (Fungal Functional Guild) analysis revealed that most of the fungal species present in the GIT are saprotroph, plant pathogen, and animal endosymbiont. Our study is the first to report that even under the same condition, large variations in fungal composition in the host GIT still occur from batch-to-batch and sampling time. The implications of our observations serve as references to the development of better models of the human gut.

Diabetic foot ulcers cause great suffering and are costly for the healthcare system. Normal wound healing involves hemostasis, inflammation, proliferation, and remodeling. However, the negative factors associated with diabetes, such as bacterial biofilms, persistent inflammation, impaired angiogenesis, inhibited cell proliferation, and pathological scarring, greatly interfere with the smooth progress of the entire healing process. It is this impaired wound healing that leads to diabetic foot ulcers and even amputations. Therefore, drug screening is challenging due to the complexity of damaged healing mechanisms. The establishment of a scientific and reasonable animal experimental model contributes significantly to the in-depth research of diabetic wound pathology, prevention, diagnosis, and treatment. In addition to the low cost and transparency of the embryo (for imaging transgene applications), zebrafish have a discrete wound healing process for the separate study of each stage, resulting in their potential as the ideal model animal for diabetic wound healing in the future. In this review, we examine the reasons behind the delayed healing of diabetic wounds, systematically review various studies using zebrafish as a diabetic wound model by different induction methods, as well as summarize the challenges and improvement strategies which provide references for establishing a more reasonable diabetic wound zebrafish model.

In spite of the growing attention given to medaka (Oryzias latipes) as an excellent vertebrate model, an effective gene knockdown system has not yet been established using cultured cells of this fish species. In this study, a gene knockdown system using short interfering RNA (siRNA) in medaka cell lines was established through the optimization of transfection conditions. By extensive screening of several medaka cell lines and transfection reagents, OLHNI-2 cells and X-tremeGENE siRNA Transfection Reagent were selected as the best combination to achieve high transfection efficiency of siRNA without cytotoxic effect. Knockdown conditions were then refined using the endogenous heat shock protein 90 (Hsp90) genes as the siRNA targets. Among the parameters tested, cell density, serum concentration in the culture medium, and duration of transfection improved knockdown efficiency, where the target mRNA in cells transfected with each of the siRNAs was reduced from 12.0% to 26.7% of the control level. Our results indicate that the established knockdown system using siRNA is a promising tool for functional analysis of medaka genes in vitro. [ABSTRACT FROM AUTHOR]

Abstract Background Coral reefs have sustained damage of increasing scale and frequency due to climate change, thereby intensifying the need to elucidate corals’ biological characteristics, including their thermal tolerance and microbial symbioses. The sea anemone, Exaiptasia diaphana, has proven an ideal coral model for many studies due to its close phylogenetic relationship and shared traits, such as symbiosis with algae of the family Symbiodiniaceae. However, established E. diaphana clonal lines are not available in Australia thus limiting the ability of Australian scientists to conduct research with this model. To help address this, the bacterial and Symbiodiniaceae associates of four Great Barrier Reef (GBR)-sourced E. diaphana genotypes established in laboratory aquaria and designated AIMS1–4, and from proxies of wild GBR E. diaphana were identified by metabarcoding of the bacterial 16S rRNA gene and eukaryotic rRNA gene ITS2 region. The relationship between AIMS1–4 and their bacterial associates was investigated, as was bacterial community phenotypic potential. Existing data from two existing anemone clonal lines, CC7 and H2, were included for comparison. Results Overall, 2238 bacterial amplicon sequence variants (ASVs) were observed in the AIMS1–4 bacterial communities, which were dominated by Proteobacteria and Bacteroidetes, together comprising > 90% relative abundance. Although many low abundance bacterial taxa varied between the anemone genotypes, the AIMS1–4 communities did not differ significantly. A significant tank effect was identified, indicating an environmental effect on the microbial communities. Bacterial community richness was lower in all lab-maintained E. diaphana compared to the wild proxies, suggesting a reduction in bacterial diversity and community phenotypic potential due to culturing. Seventeen ASVs were common to every GBR lab-cultured anemone, however five were associated with the Artemia feedstock, making their specific association to E. diaphana uncertain. The dominant Symbiodiniaceae symbiont in all GBR anemones was Breviolum minutum. Conclusion Despite differences in the presence and abundance of low abundance taxa, the bacterial communities of GBR-sourced lab-cultured E. diaphana are generally uniform and comparable to communities reported for other lab-cultured E. diaphana. The data presented here add to the global E. diaphana knowledge base and make an important contribution to the establishment of a GBR-sourced coral model organism.

Urodele amphibian newts have unique biological properties in male gametogenesis, in addition to their extreme regenerative capacity. Male newts are able to regenerate new testes even after reaching sexual maturity and can possess multiple testes. Notably, these animals maintain primordial germ cell‐like cells in a tissue adjacent to the testis. Spermatogenesis proceeds while synchronizing in a region‐specific manner in the testis. However, the newt species that have been used most commonly require 2–3 years to achieve sexual maturity, and spermatogenesis in these species shows seasonality. These traits have restricted the use of newts for studies on testicular development and spermatogenesis, and testis development in newts remains poorly characterized. Recently, the Iberian ribbed newt Pleurodeles waltl has been established as an emerging model organism. P. waltl reaches sexual maturity more quick after birth than do other newts and is capable of breeding year‐round. Thus, P. waltl is expected to serve as an appealing experimental model for studying the mechanisms of male gametogenesis in the urodeles. In the present study, we use P. waltl to describe the entire developmental process of the newt testis from primordial gonad to maturity. Notably, the mature testes show synchronized progression of spermatogenesis along the anteroposterior axis. Additionally, we demonstrate that the process of spermatogenesis in P. waltl proceeds irrespective of day length. Our results show that P. waltl newts are a suitable model for investigating the process of testicular development. We also expect that these results will be useful for the maintenance of P. waltl bioresources. [ABSTRACT FROM AUTHOR]

Urate oxidase (uricase, Uox) is a big obstacle for scientists to establish stable animal models for studying hyperuricemia and associated disorders. Due to the low survival rate of uricase-deficient mice, we generated a Uox-knockout model animal from Sprague Dawley (SD) rats using the CRISPR/Cas9 technique by deleting exons 2 to 4 of the Uox gene. The uricase-deficient rats were named “Kunming-DY rats”, and were apparently healthy with more than a 95% survival up to one year. The male rats’ serum uric acid (SUA) increased to 48.3 ± 19.1 µg/ml, significantly higher than those of wild-type rats. Some indexes of the blood fat like total triglyceride, low density lipoprotein, and renal function indexes including blood urea nitrogen and serum creatinine were significantly different from those of wild-type rats, however, all the indexes were close to or in normal ranges. Histological renal changes including mild glomerular/tubular lesions were observed in these uricase-deficient rats. Thus, “Kunming-DY rats” with stable uricase-deficiency were successfully established and are an alternative model animal to study hyperuricemia and associated diseases mimicking human conditions.

Purpose: This study analyzes the structures of optic nerve elements, i.e., glial cells and nerve fibers, in an STZ-induced hyperglycemic animal model. Morphological changes in glial elements of the optic nerve in hyperglycemic and normoglycemic animals were compared. Methods: Transmission electron microscopy, histochemistry, immunohistochemistry, and morphometry were used in this study. Results: Hyperglycemia increased the numbers of inner mesaxons and axons with degenerative profiles. Furthermore, it led to both an increase in the amount of debris and in the numbers of secondary lysosomic vesicles in glial cytoplasm. Hyperglycemia also led to a decrease in glial fibrillary acidic protein expression and an increase in periodic acid-Schiff-positive deposits in the optic nerves of hyperglycemic animals. Conclusion: We conclude that the damage to the structural elements observed in our animal models contributes to the pathogenesis of optic neuropathy in the early stages of diabetes.

Abstract Background The mangrove killifish Kryptolebias marmoratus is the only vertebrate that reproduces by self-fertilizing and is an important model species in genetics and marine ecotoxicology. Using whole-genome and transcriptome sequences, we identified all members of the cytochrome P450 (CYP) family in this model teleost and compared them with those of other teleosts. Results A total of 74 cytochrome P450 genes and one pseudogene were identified in K. marmoratus. Phylogenetic analysis indicated that the CYP genes in clan 2 were most expanded, while synteny analysis with other species showed orthologous relationships of CYP subfamilies among teleosts. In addition to the CYP2K expansions, five tandem duplicated gene copies of CYP5A were observed. These features were unique to K. marmoratus. Conclusions These results shed a light on CYP gene evolution, particularly the co-localized CYP2K, CYP5A, and CYP46A subfamilies in fish. Future studies of CYP expression could identify specific endogenous and exogenous environmental factors that triggered the evolution of tandem CYP duplication in K. marmoratus.

This study sought to monitor the dynamic process of lymph node (LN) metastasis with intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI), and to investigate the impact of disease course on the detection of metastatic LNs by IVIM-DWI. Twenty female New Zealand rabbits with 2.5–3.0 kg body weight were studied. VX2 cells and egg yolk emulsion were randomly inoculated into one thigh to induce metastatic and inflammatory popliteal LNs, respectively. Eight rabbits underwent IVIM-DWI (14 b values, 0–2000 s/mm2) 2 h prior to, and 14, 21, and 28 days after inoculation (D0, D14, D21, D28). The apparent diffusion coefficient (ADC), true diffusion coefficient (D), pseudodiffusion coefficient (D*), and perfusion fraction (f) were measured and compared between the metastatic and the inflammatory groups at each time point. Three rabbits randomly chosen from the remaining twelve rabbits were sacrificed at each time point to perform hematoxylin and eosin staining and histologic evaluation. The patterns of dynamic change of D*, ADC, and D were different between the metastatic and the inflammatory LNs. The metastatic group had a lower D* value at D14 (p =.003), and greater ADC and D values at both D21 (p =.001, p =.001) and D28 (p =.021, p =.001), compared to the inflammatory group. The f value of the metastatic group was greater than that of the inflammatory only at D28 (p =.001). IVIM-DWI can reflect the dynamic process of LN metastasis, and disease course has a significant influence on the ability of IVIM-DWI to detect metastatic nodes. [ABSTRACT FROM AUTHOR]

Ionising radiation causes the death of the most actively dividing cells, thus leading to depletion of the stem cell pool. Planarians are invertebrate flatworms that are unique in that their stem cells, called neoblasts, constantly replace old, damaged, or dying cells. Amenability to efficient RNAi treatments, the rapid development of clear phenotypes, and sensitivity to ionising radiation, combined with new genomic technologies, make planarians an outstanding tool for the discovery of potential radioprotective agents. In this work, using the well-known antioxidant N-acetylcysteine, planarians are, for the first time, shown to be an excellent model system for the fast and effective screening of novel radioprotective and radio-sensitising substances. In addition, a panel of measurable parameters that can be used for the study of radioprotective effects on this model is suggested.

Abstract Background Bortezomib (Bz) is a proteasome inhibitor that directly targets antibody-producing plasma cells. We recently reported the first randomized control trial that evaluated the effects of Bz in patients with systemic lupus erythematosus (SLE). In that study, we demonstrated that Bz treatment is associated with many adverse reactions in patients with refractory disease. In the present study, we examine the therapeutic and toxic effects of Bz on MRL/MpJ-lpr/lpr (MRL/lpr) mice with severe disease activity. Methods Female MRL/lpr mice at 10 and 14 weeks of age were treated with phosphate buffered saline (PBS) (n = 19), Bz (750 μg/kg twice weekly) (n = 27), or cyclophosphamide (Cyc) (1 mg/body, once in 2 weeks) (n = 20). Cellular subsets, serum immunoglobulin, anti-double-stranded DNA (anti-dsDNA) antibody titer, and a pathological index of glomerulonephritis were then analyzed at 22 weeks of age. Survival curves of the 10-week-old and 14-week-old Bz-treated groups were compared. Blood counts, creatinine, liver enzymes, and serum cytokine levels were measured 1 week after Bz treatment. Gene expression profiling of spleens from Bz and Cyc treatment mice were compared with those from control mice. Results The anti-dsDNA antibody levels were significantly higher in 14-week-old than in 10-week-old mice, indicating a higher disease activity at 14 weeks. A significant decrease in the number of splenic cells and glomerulonephritis index was observed in Bz-treated and Cyc-treated mice. Bz, but not Cyc, significantly decreased serum immunoglobulin and anti-dsDNA antibody titer levels. Survival curve analysis revealed a significantly higher mortality rate in 14-week-old than in 10-week-old Bz-treated and control groups. Following two injections of Bz, serum IL-6 and TNF-α levels were significantly more elevated in 14-week-old than in 10-week-old mice. Potentially immunogenic molecules, such as heat shock proteins, were characteristically upregulated in spleens of Bz-treated but not Cyc-treated mice. Conclusions In spite of its therapeutic effect, Bz treatment had more toxic effects associated with increased proinflammatory cytokine levels in mice with a higher disease activity. Understanding the mechanism of the toxicity and developing preventive strategies against it is important for the safe clinical application of Bz in human SLE.

Brown adipose tissue (BAT) contributes to non-shivering thermogenesis and plays an important role in body temperature control. The contribution of BAT thermogenesis to body temperature control in a non-cold environment was evaluated using developing hamsters. Immunostaining for uncoupling protein 1 (UCP1), a mitochondrial protein responsible for BAT thermogenesis, indicated that interscapular fat tissue had matured as BAT at day 14. When pups were placed on a thermal plate kept at 23°C, the body surface temperature decreased in day 7- and 10-day-old pups but was maintained at least for 15 min in 14-day-old pups, indicating that hamsters are unable to maintain their body temperature until around day 14 even in a non-cold environment. Body temperature maintenance was also evaluated in UCP1-deficient mice. BAT analysis showed that the UCP1 protein level in Ucp1+/− Hetero mice was 61.3 ± 1.4% of that in wild-type (WT) mice and was undetected in Ucp1−/− knockout (KO) mice. When 12-day-old pups were place on a thermal plate at 23°C, body surface temperature was maintained for at least 15 min in WT and Hetero mice but gradually dropped by 2.4 ± 0.2°C in 15 min in KO mice. It is concluded that BAT thermogenesis is indispensable for body temperature maintenance in pups of hamsters and mice, even in the non-cold circumstances. The early life poikilothermy and the later acquirement of homeothermy in hamsters may be because of the postnatal development of BAT. [ABSTRACT FROM AUTHOR]

Background: We hypothesized that an ideal heart valve replacement would be acellular valve root scaffolds seeded with autologous stem cells. To test this hypothesis, we prepared porcine acellular pulmonary valves, seeded them with autologous adipose derived stem cells (ADSCs) and implanted them in sheep and compared them to acellular valves.

Caenorhabditis elegans has been used in research for years to clarify the genetic cascades and molecular mechanisms of aging, longevity, and health span. Health span is closely related to frailty; however, frailty has a different concept and is evaluated using various parameters in humans, such as Fried's Frailty Criteria. The C. elegans model has several advantages when performing a chemical screen to identify drug candidates. Several mouse models of frailty were recently developed, including a homozygous IL-10 knockout. These mouse models are useful for understanding human frailty; however, they are not appropriate for primary drug screening because they require large spaces, expensive cost, and time consuming assessments. Therefore, a combination of these models may be a promising tool for discovering drugs and understanding the mechanisms of frailty. In addition, natural products, and herbs are attractive sources of novel drugs with pharmacological activity and low toxicity, in fact, over 60% of currently-available drugs are estimated to be related to natural compounds. In this review, the possibility of identifying natural agents (i.e., herb extracts and compounds) that could improve frailty are proposed, and the advantages and limitations of these models are also discussed.

To establish an entirely cerebrospinal fluid (CSF)-contacting nucleus-deficient model animal, we used cholera toxin B subunit (CB)- saporin (SAP), which is an analog of CB-HRP that specifically labels the CSF-contacting nucleus, to exclusively damage the nucleus. The effectiveness and specificity of the ablation were evaluated upon days 1–10 after CB-SAP microinjection into the brain ventricular system. The vital status, survival, and common physiological parameters of the model animals were also assessed during the experimental period. The results demonstrated that CB-SAP damaged only the CSF-contacting nucleus, but not other functional structures, in the brain. The complete ablation occurred by day 7 after CB-SAP microinjection. A model animal that had no CSF-contacting nucleus was established after survival beyond that time point. No obvious effects were observed in the vital status of the model animals, and their survival was ensured. The common physiological parameters of model animals were stable. The present study provides a method to establish a CSF-contacting nucleus “knockout” model animal, which is similar to a gene knockout model animal for studying this particular nucleus in vivo.

To establish an entirely cerebrospinal fluid (CSF)-contacting nucleus-deficient model animal, we used cholera toxin B subunit (CB)- saporin (SAP), which is an analog of CB-HRP that specifically labels the CSF-contacting nucleus, to exclusively damage the nucleus. The effectiveness and specificity of the ablation were evaluated upon days 1-10 after CB-SAP microinjection into the brain ventricular system. The vital status, survival, and common physiological parameters of the model animals were also assessed during the experimental period. The results demonstrated that CB-SAP damaged only the CSF-contacting nucleus, but not other functional structures, in the brain. The complete ablation occurred by day 7 after CB-SAP microinjection. A model animal that had no CSF-contacting nucleus was established after survival beyond that time point. No obvious effects were observed in the vital status of the model animals, and their survival was ensured. The common physiological parameters of model animals were stable. The present study provides a method to establish a CSF-contacting nucleus "knockout" model animal, which is similar to a gene knockoutmodel animal for studying this particular nucleus in vivo. [ABSTRACT FROM AUTHOR]

Background: The mangrove killifish Kryptolebias marmoratus is the only vertebrate that reproduces by self-fertilizing and is an important model species in genetics and marine ecotoxicology. Using whole-genome and transcriptome sequences, we identified all members of the cytochrome P450 (CYP) family in this model teleost and compared them with those of other teleosts. Results: A total of 74 cytochrome P450 genes and one pseudogene were identified in K. marmoratus. Phylogenetic analysis indicated that the CYP genes in clan 2 were most expanded, while synteny analysis with other species showed orthologous relationships of CYP subfamilies among teleosts. In addition to the CYP2K expansions, five tandem duplicated gene copies of CYP5A were observed. These features were unique to K. marmoratus. Conclusions: These results shed a light on CYP gene evolution, particularly the co-localized CYP2K, CYP5A, and CYP46A subfamilies in fish. Future studies of CYP expression could identify specific endogenous and exogenous environmental factors that triggered the evolution of tandem CYP duplication in K. marmoratus. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) is a continuous disease spectrum characterized by the accumulation of excessive lipid in hepatocytes. Simple hepatic steatosis may progress to NAFLD and even liver fibrosis . liver cirrhosis, and finally hepatocellular carcinoma. Animal models can simulate different causes and histopathological and pathophysiological changes in each stage of NAFLD and thus provide critical guidance for understanding the pathogenesis of NAFLD and selecting therapeutic measures. At present, there are still no ideal animal models that can simulate the whole disease spectrum. This article introduces the most frequently used and recently developed animal models for NAFLD and NAFLD - induced liver cancer and summarizes possible therapeutic targets with reference to the experimental pathogenesis of NAFLD in animal models, in order to provide a basis for further research on the pathogenesis and treatment of NAFLD. [ABSTRACT FROM AUTHOR]

Tremor dominant Kyoto ( Trdk ) is an autosomal dominant mutation that appeared in F344/NSlc rats mutagenized with N -ethyl- N -nitrosourea (ENU). In this study, we characterized and genetically analyzed F344- Trdk /+ heterozygous rats. The rats exhibited a tremor that was especially evident around weaning but persisted throughout life. The tremors of F344- Trdk /+ rats were attenuated by drugs effective against essential tremor (ET) but not drugs used to treat Parkinson’s disease–related tremor, indicating that the pharmacological phenotype of F344- Trdk /+ rats was similar to human ET. Using positional candidate approach, we identified the Trdk mutation as a missense substitution (c. 866 T > A, p. I289N) in Kcnn2, which encodes the SK2 subunit of the small-conductance Ca 2+ -activated K + channel. In vitro electrophysiological studies revealed that the I289N mutation diminished SK2 channel activity. These findings demonstrate that F344- Trdk /+ rats represent a novel model of ET, and strongly suggest that Kcnn2 is the causative gene for the tremor phenotype in F344- Trdk /+ rats. [ABSTRACT FROM AUTHOR]

Pain phenomenon, the unpleasant sensory and emotional event, appears to evidently intrude in Parkinson disease (PD), a disease formally considered to be restricted only to motor deficits. Although over a half of persons with PD suffer from pain manifestations, there are very few reports targeting this issue. Considering the cases when motor symptoms of PD are eclipsed by severe pain disclosure, there is an obvious need of clarifying the intricate implications of pain in PD context. Because there are few studies researching the link between pain and PD in clinical context, but as well in animal models we chose to explore the effects of pain stimuli on a rodent model of PD. Materials and methods: We experimentally induced a PD model in Wistar rats (n=12) by injecting in the substantia nigra, a brain area known to be involved in PD occurrence, one dose of a 6-hydroxidopamine (6-OHDA) solution (8μm 6-OHDA base and 4μm physiological saline), utilizing neurosurgery, while their control peers received same dose of saline solution. Two weeks after the intervention the animals were subjected to the hot-plate test, a behavioral task for acquiring pain sensitivity. Results: There was noticed a statistical significant (F(1,10) = 5.67, p=0.038) sensibility of the 6-OHDA rats to thermal pain stimuli (8.2 s ± 0.8 s in 6-OHDA group) as compared to their peers (13.8 s ± 1.6 s in controls). Conclusions: The involvement of pain in PD animal models is demonstrated raising questions of how it influences PD evolution. Moreover, this result increases awareness of deficient diagnostic methods of pain in PD and as a consequence, poor treatment of pain manifestations. [ABSTRACT FROM AUTHOR]

The Fat Sand Rat (Psammomys obesus, P. obesus) is a diurnal herbivore and phytophage, with seasonal reproductive behavior. The sexually active phase lasts from autumn to early spring and the sexually inactive phase from late spring to summer. In the past years, P. obesus has gained much attention as an animal model in biological and clinical research. It is a suitable model for diet-induced insulin resistance, non-insulin-dependent diabetes mellitus and obesity studies. In addition, the seasonal reproduction of P. obesus is gaining more and more attention. The current paper aims to review and sum up the progress in the understanding of the reproductive anatomo-histo-physiology of Psammomys obesus , in order to facilitate future research in this area and to expose further perspectives for researchers. • Psammomys obesus is a valuable animal model for biological and clinical research. • It is a suitable model for diet-induced insulin resistance, non-insulin-dependent diabetes mellitus and obesity studies. • The reproductive behavior of P. obesus corresponds to an ecophysiological adaptation. • P. obesus represents a suitable model for studying the mechanism of environmental restricted reproduction. [ABSTRACT FROM AUTHOR]

We analyzed the heartbeat interval to test the possibility that the detrended fluctuation analysis (DFA) distinguishes a sick condition from a healthy condition of the cardiac control network. The healthy heart exhibited exponents ranging from 0.8 to 1.0 in both, animal models and humans. In the sick animal models, the exponents declined with an approaching very low range leading to a natural death (~0.6 in the end). Other models, which had a myocardial injury, exhibited extremely high exponents (~1.4). The high exponent was maintained until they died. Human arrhythmic hearts exhibited low exponent (~0.7). A human subject who has an abnormally high heart rate exhibited high exponents (as high as 1.4). A Human transplanted heart, which has no nervous controls, exhibited exponent 1.2. The fluctuation of the heartbeat interval contains information for the risk of a cardiac cessation or mortality.

Desialylation in the lysosome is a crucial step for glycoprotein degradation. The abnormality of lysosomal desialylation by NEU1 sialidase is involved in diseases of mammals such as sialidosis and galactosialidosis. Mammalian Neu1 sialidase is also localized at plasma membrane where it regulates several signaling pathways through glycoprotein desialylation. In fish, on the other hand, the mechanism of desialylation in the lysosome and functions of Neu1 sialidase are still unclear. Here, to understand the significance of fish Neu1 sialidase, neu1 gene was cloned from medaka brain and the profiles of its polypeptides were analyzed. Open reading frame of medaka neu1 consisted 1,182 bp and the similarity of its deduced amino acids with human NEU1 was 57%. As this recombinant polypeptide did not show significant sialidase activity, medaka cathepsin A, known in mammals as protective protein activating Neu1, was cloned and then co-expressed with medaka Neu1 to examine whether medaka cathepsin A activates Neu1 activity. As a result, Neu1/cathepsin A showed a drastic increase of sialidase activity toward MU-NANA. Major substrate of medaka Neu1 was 3-sialyllactose and its optimal pH was 4.0. With immunofluorescence analysis, signal of overexpressed medaka Neu1 was found to coincide with Lysotracker signals (organelle marker of lysosome) and co-localized with medaka cathepsin A in fish hepatic Hepa-T1 cells. Furthermore, part of medaka Neu1 was also detected at plasma membrane. Medaka Neu1 possessed signal peptide sequence at N-terminal and incomplete lysosomal targeting sequence at C-terminus. Medaka neu1 gene was ubiquitously expressed in various medaka tissues, and its expression level was significantly higher than other sialidase genes such as neu3a , neu3b and neu4 . The present study revealed the profiles of fish Neu1 sialidase and indicated its high conservation with human NEU1 for the first time, suggesting the presence of similar desialylation system in the medaka lysosome to human. Moreover, the present study showed the possibility of medaka as a model animal of human NEU1 sialidase. [ABSTRACT FROM AUTHOR]

The purpose of this experimental model with rabbits is investigating the variation of blood flow in the expanded skin versus expansion time. New Zealand breed rabbits are used. Two groups are studied: F-1 receiving expanders on the right tight and F-2 receiving expanders bilateraly. Progressively, five expansions are performed. The first radioiosotopic perfusional evaluation is performed just after the surgery and the following evaluation are performed at the second, sixth, thirteenth, twentieth and twenty-seventh post-surgical days. As radiotracer, technetium 99m are used in the chemical form of sodium pertechnetate. Scintillographic images are obtained by CGR scintillation camera. The quantitative analysis is done by calculation of the reperfusion rate.Este modelo experimental em coelhos tem como proposição investigar a variação do fluxo sanguíneo na pele expandida em relação ao tempo de expansão. Utilizam-se coelhos da raça Nova Zelândia. Estudam-se dois grupos: F-1 que recebe expansor na coxa direita e F-2 que recebe expansores bilateralmente. São feitas progressivamente cinco expansões. Realiza-se a primeira avaliação perfusional radioisotópica logo após o ato operatório e as seguintes no segundo, sexto, décimo-terceiro, vigésimo e vigésimo-sétimo dia pós-operatórios. Utiliza-se como radiotraçador o tecnécio 99m na forma química de pertecnetato de sódio. Obtêm-se as imagens cintilográficas em câmara de cintilação CGR. Faz-se a análise quantitativa pelo cálculo do Índice de reperfusão.

As the human lifespan has increased dramatically in recent decades, the amount of aging research has correspondingly increased. To investigate mechanisms of aging, an efficient model system is required. Although mammalian animal models are essential for aging studies, they are sometimes inappropriate due to their long lifespans and high maintenance costs. In this regard, insects can be effective alternative model systems for aging studies, as insects have a relatively short lifespan and cost less to maintain. Many species of insects have been used as model systems for aging studies, especially fruit flies, silkworm moths and several social insects. Fruit flies are most commonly used for aging studies due to the wide availability of abundant resources such as mutant stocks, databases and genetic tools. Silkworm moths are also good tools for studying aging at the tissue level due to their relatively large size. Last, social insects such as ants and bees are good for investigating lifespan determinants, as their lifespans significantly differ according to caste despite a constant genotype among the population. In this review, we discuss the current status and future prospects of aging research using insect model systems. [ABSTRACT FROM AUTHOR]

The need for nonmammalian and nonvertebrate experimental systems for toxicology is increasing because of growing concern about animal welfare. Hydra, a genus of freshwater cnidarian, has been used in classical toxicology for more than 40 years and has been recommended as a standard model for ecotoxicology. Functional assays using Hydra homologues of the signal molecules and transcription factors of other metazoans have demonstrated that Hydra shares the common molecular mechanisms for pattern formation with bilaterian animals. The availability of the Hydra genome and mRNA information has meant that it can be used as a model organism in biological sciences. The purpose of this review is to explore recent developments in our understanding of the molecular aspects of axis formation, bud formation, regeneration, and the nervous system in Hydra and to introduce Hydra as an alternative animal model in environmental toxicogenomics for predicting the toxicity of environmental pollutants at the molecular level. [ABSTRACT FROM AUTHOR]

This study estimated the genetic vari-ance components of P utilization in Japanese quail. A parental generation was assembled from an unselected random-bred Japanese fattening quail line. Seven sires and 14 dams were randomly selected, and each sire was paired with 2 dams to produce full and half sibs. A total of 200 unsexed 1-d-old quail with known pedigree were wing-banded and raised during the first 4 d post-hatch in groups in floor pens on wood shavings and fed a preexperimental diet that was adequate in all nutri-ents. Starting on d 5, quail were individually housed in metabolic compartments on P-free filter paper. This started a balance trial with 5 d of adaption and 5 d of total excreta collection. During this balance period, all quail were fed a low-P (3.9 g/kg of DM) corn-soybean meal-based diet with a Ca:P ratio of 1.6:1.0. Phospho-rus and Ca utilization were determined individually us-ing the difference in P or Ca intake and the total P or Ca excretion. The average P utilization was 72% and the average Ca utilization was 63%, each with very high variation. Heritabilities were estimated to be 0.09 (SE = 0.09) for P utilization and 0.09 (SE = 0.09) for Ca utilization. Heritabilities were close to the values reported in the literature for broilers and suggest that quail are suitable as a model animal. The SE of the her-itability estimates were large. This implies that further studies with a larger sample size are needed to identify genetic and physiological mechanisms that influence P and Ca utilization in Japanese quail. [ABSTRACT FROM AUTHOR]