8 results on '"Rathje CC"'
Search Results
2. The contribution of sex chromosome conflict to disrupted spermatogenesis in hybrid house mice.
- Author
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Kopania EEK, Watson EM, Rathje CC, Skinner BM, Ellis PJI, Larson EL, and Good JM
- Subjects
- Humans, Male, Mice, Animals, Spermatogenesis genetics, Sex Chromosomes genetics, X Chromosome genetics, Hybridization, Genetic, Infertility, Male genetics
- Abstract
Incompatibilities on the sex chromosomes are important in the evolution of hybrid male sterility, but the evolutionary forces underlying this phenomenon are unclear. House mice (Mus musculus) lineages have provided powerful models for understanding the genetic basis of hybrid male sterility. X chromosome-autosome interactions cause strong incompatibilities in M. musculus F1 hybrids, but variation in sterility phenotypes suggests a more complex genetic basis. In addition, XY chromosome conflict has resulted in rapid expansions of ampliconic genes with dosage-dependent expression that is essential to spermatogenesis. Here, we evaluated the contribution of XY lineage mismatch to male fertility and stage-specific gene expression in hybrid mice. We performed backcrosses between two house mouse subspecies to generate reciprocal Y-introgression strains and used these strains to test the effects of XY mismatch in hybrids. Our transcriptome analyses of sorted spermatid cells revealed widespread overexpression of the X chromosome in sterile F1 hybrids independent of Y chromosome subspecies origin. Thus, postmeiotic overexpression of the X chromosome in sterile F1 mouse hybrids is likely a downstream consequence of disrupted meiotic X-inactivation rather than XY gene copy number imbalance. Y chromosome introgression did result in subfertility phenotypes and disrupted expression of several autosomal genes in mice with an otherwise nonhybrid genomic background, suggesting that Y-linked incompatibilities contribute to reproductive barriers, but likely not as a direct consequence of XY conflict. Collectively, these findings suggest that rapid sex chromosome gene family evolution driven by genomic conflict has not resulted in strong male reproductive barriers between these subspecies of house mice., (© The Author(s) 2022. Published by Oxford University Press on behalf of Genetics Society of America. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
- Published
- 2022
- Full Text
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3. The Economic Burden of Chromosome Translocations and the Benefits of Enhanced Screening for Cattle Breeding.
- Author
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Lewis NM, Canedo-Ribeiro C, Rathje CC, Jennings RL, Danihel M, Bosman LM, Silvestri G, and Griffin DK
- Abstract
The cattle breeding industry, through both of its derivatives (dairy and beef), provides 81% of milk and 22% of meat required globally. If a breeding bull is sub-fertile, this impacts herd conception and birth rates, and it is generally accepted that having a proactive genetic screening programme can prevent further losses. Chromosome translocations are the leading genetic cause of infertility in livestock and, in cattle, this extends beyond the classical 1:29 to other Robertsonian translocations (RobTs) and to reciprocal translocations (RECTs). The incidence of both (collectively termed RTs) varies between breeds and herds; however, we estimate that RECTs are, most likely, at least twice as common as RobTs. The purpose of this study was to develop an industry economic model to estimate the financial impact of an RT event at the herd level. If we assume a conservative incidence rate of 0.4% for Rob1:29 with each one impacting the conception rate by 5%, we calculate that actively screening for and removing a Rob1:29 bull could benefit an impacted herd by GBP 2.3 million (approx. USD 2.8 million) over six years. A recently updated screening protocol developed in our lab for all RTs, however (with a projected combined incidence of 1.2%, impacting conception rates by 10%), could benefit an impacted herd by GBP 7.2 million (nearly USD 9 million) for each RT found. For an industry worth USD 827.4 billion (dairy) and USD 467.7 billion (beef), expanding knowledge on incidence and further dissection of the potential costs (financial and environmental) from RTs is essential to prevent further losses.
- Published
- 2022
- Full Text
- View/download PDF
4. Rapid Multi-Hybridisation FISH Screening for Balanced Porcine Reciprocal Translocations Suggests a Much Higher Abnormality Rate Than Previously Appreciated.
- Author
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O'Connor RE, Kiazim LG, Rathje CC, Jennings RL, and Griffin DK
- Subjects
- Animals, Chromosome Banding, Chromosomes, Mammalian genetics, Metaphase, In Situ Hybridization, Fluorescence, Swine genetics, Translocation, Genetic
- Abstract
With demand rising, pigs are the world's leading source of meat protein; however significant economic loss and environmental damage can be incurred if boars used for artificial insemination (AI) are hypoprolific (sub-fertile). Growing evidence suggests that semen analysis is an unreliable tool for diagnosing hypoprolificacy, with litter size and farrowing rate being more applicable. Once such data are available, however, any affected boar will have been in service for some time, with significant financial and environmental losses incurred. Reciprocal translocations (RTs) are the leading cause of porcine hypoprolificacy, reportedly present in 0.47% of AI boars. Traditional standard karyotyping, however, relies on animal specific expertise and does not detect more subtle (cryptic) translocations. Previously, we reported development of a multiple hybridisation fluorescence in situ hybridisation (FISH) strategy; here, we report on its use in 1641 AI boars. A total of 15 different RTs were identified in 69 boars, with four further animals XX/XY chimeric. Therefore, 4.5% had a chromosome abnormality (4.2% with an RT), a 0.88% incidence. Revisiting cases with both karyotype and FISH information, we reanalysed captured images, asking whether the translocation was detectable by karyotyping alone. The results suggest that chromosome translocations in boars may be significantly under-reported, thereby highlighting the need for pre-emptive screening by this method before a boar enters a breeding programme.
- Published
- 2021
- Full Text
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5. Differential Sperm Motility Mediates the Sex Ratio Drive Shaping Mouse Sex Chromosome Evolution.
- Author
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Rathje CC, Johnson EEP, Drage D, Patinioti C, Silvestri G, Affara NA, Ialy-Radio C, Cocquet J, Skinner BM, and Ellis PJI
- Subjects
- Animals, Male, Mice, Sex Ratio, Biological Evolution, Sex Chromosomes physiology, Sperm Motility, Spermatozoa physiology, Y Chromosome genetics
- Abstract
The mouse sex chromosomes exhibit an extraordinary level of copy number amplification of postmeiotically expressed genes [1, 2], driven by an "arms race" (genomic conflict) between the X and Y chromosomes over the control of offspring sex ratio. The sex-linked ampliconic transcriptional regulators Slx and Sly [3-7] have opposing effects on global transcription levels of the sex chromosomes in haploid spermatids via regulation of postmeiotic sex chromatin (PMSC) [8-11] and opposing effects on offspring sex ratio. Partial deletions of the Y chromosome (Yq) that reduce Sly copy number lead to global overexpression of sex-linked genes in spermatids and either a distorted sex ratio in favor of females (smaller deletions) or sterility (larger deletions) [12-16]. Despite a large body of work studying the role of the sex chromosomes in regulating spermatogenesis (recent reviews [17-20]), most studies do not address differential fertility effects on X- and Y-bearing cells. Hence, in this study, we concentrate on identifying physiological differences between X- and Y-bearing sperm from Yq-deleted males that affect their relative fertilizing ability and consequently lead to sex ratio skewing. We show that X- and Y-bearing sperm in these males have differential motility and morphology but are equally able to penetrate the cumulus and fertilize the egg once at the site of fertilization. The altered motility is thus deduced to be the proximate cause of the skew. This represents the first demonstration of a specific difference in sperm function associated with sex ratio skewing., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2019
- Full Text
- View/download PDF
6. A Conserved Requirement for Fbxo7 During Male Germ Cell Cytoplasmic Remodeling.
- Author
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Rathje CC, Randle SJ, Al Rawi S, Skinner BM, Nelson DE, Majumdar A, Johnson EEP, Bacon J, Vlazaki M, Affara NA, Ellis PJ, and Laman H
- Abstract
Fbxo7 is the substrate-recognition subunit of an SCF-type ubiquitin E3 ligase complex. It has physiologically important functions in regulating mitophagy, proteasome activity and the cell cycle in multiple cell types, like neurons, lymphocytes and erythrocytes. Here, we show that in addition to the previously known Parkinsonian and hematopoietic phenotypes, male mice with reduced Fbxo7 expression are sterile. In these males, despite successful meiosis, nuclear elongation and eviction of histones from chromatin, the developing spermatids are phagocytosed by Sertoli cells during late spermiogenesis, as the spermatids undergo cytoplasmic remodeling. Surprisingly, despite the loss of all germ cells, there was no evidence of the symplast formation and cell sloughing that is typically associated with spermatid death in other mouse sterility models, suggesting that novel cell death and/or cell disposal mechanisms may be engaged in Fbxo7 mutant males. Mutation of the Drosophila Fbxo7 ortholog, nutcracker ( ntc ) also leads to sterility with germ cell death during cytoplasmic remodeling, indicating that the requirement for Fbxo7 at this stage is conserved. The ntc phenotype was attributed to decreased levels of the proteasome regulator, DmPI31 and reduced proteasome activity. Consistent with the fly model, we observe a reduction in PI31 levels in mutant mice; however, there is no alteration in proteasome activity in whole mouse testes. Our results are consistent with findings that Fbxo7 regulates PI31 protein levels, and indicates that a defect at the late stages of spermiogenesis, possibly due to faulty spatial dynamics of proteasomes during cytoplasmic remodeling, may underlie the fertility phenotype in mice., (Copyright © 2019 Rathje, Randle, Al Rawi, Skinner, Nelson, Majumdar, Johnson, Bacon, Vlazaki, Affara, Ellis and Laman.)
- Published
- 2019
- Full Text
- View/download PDF
7. A high-throughput method for unbiased quantitation and categorization of nuclear morphology†.
- Author
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Skinner BM, Rathje CC, Bacon J, Johnson EEP, Larson EL, Kopania EEK, Good JM, Yousafzai G, Affara NA, and Ellis PJI
- Subjects
- Algorithms, Animals, Cell Nucleus physiology, Chromatin chemistry, Chromatin metabolism, Chromatin pathology, Cytological Techniques methods, Cytological Techniques veterinary, High-Throughput Screening Assays veterinary, Infertility, Male pathology, Male, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Inbred CBA, Mice, Inbred DBA, Reproducibility of Results, Semen Analysis veterinary, Software, Species Specificity, Spermatozoa pathology, Spermatozoa ultrastructure, Cell Nucleus classification, High-Throughput Screening Assays methods, Image Processing, Computer-Assisted methods, Organelle Shape, Semen Analysis methods, Spermatozoa cytology
- Abstract
The physical arrangement of chromatin in the nucleus is cell type and species-specific, a fact particularly evident in sperm, in which most of the cytoplasm has been lost. Analysis of the characteristic falciform ("hook shaped") sperm in mice is important in studies of sperm development, hybrid sterility, infertility, and toxicology. However, quantification of sperm shape differences typically relies on subjective manual assessment, rendering comparisons within and between samples difficult. We have developed an analysis program for morphometric analysis of asymmetric nuclei and characterized the sperm of mice from a range of inbred, outbred, and wild-derived mouse strains. We find that laboratory strains have elevated sperm shape variability both within and between samples in comparison to wild-derived inbred strains, and that sperm shape in F1 offspring from a cross between CBA and C57Bl6J strains is subtly affected by the direction of the cross. We further show that hierarchical clustering can discriminate distinct sperm shapes with greater efficiency and reproducibility than even experienced manual assessors, and is useful both to distinguish between samples and also to identify different morphological classes within a single sample. Our approach allows for the analysis of nuclear shape with unprecedented precision and scale and will be widely applicable to different species and different areas of biology., (© The Authors 2019. Published by Oxford University Press on behalf of Society for the Study of Reproduction.)
- Published
- 2019
- Full Text
- View/download PDF
8. Automated Nuclear Cartography Reveals Conserved Sperm Chromosome Territory Localization across 2 Million Years of Mouse Evolution.
- Author
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Skinner BM, Bacon J, Rathje CC, Larson EL, Kopania EEK, Good JM, Affara NA, and Ellis PJI
- Subjects
- Animals, Automation methods, Cell Nucleus ultrastructure, Male, Mice, Spermatozoa cytology, Cell Nucleus genetics, Chromosome Painting methods, Evolution, Molecular, Sex Chromosomes genetics
- Abstract
Measurements of nuclear organization in asymmetric nuclei in 2D images have traditionally been manual. This is exemplified by attempts to measure chromosome position in sperm samples, typically by dividing the nucleus into zones, and manually scoring which zone a fluorescence in-situ hybridisation (FISH) signal lies in. This is time consuming, limiting the number of nuclei that can be analyzed, and prone to subjectivity. We have developed a new approach for automated mapping of FISH signals in asymmetric nuclei, integrated into an existing image analysis tool for nuclear morphology. Automatic landmark detection defines equivalent structural regions in each nucleus, then dynamic warping of the FISH images to a common shape allows us to generate a composite of the signal within the entire cell population. Using this approach, we mapped the positions of the sex chromosomes and two autosomes in three mouse lineages ( Mus musculus domesticus , Mus musculus musculus and Mus spretus ). We found that in all three, chromosomes 11 and 19 tend to interact with each other, but are shielded from interactions with the sex chromosomes. This organization is conserved across 2 million years of mouse evolution., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.
- Published
- 2019
- Full Text
- View/download PDF
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