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Gene targeting in embryonic stem cells is employed to generate beta-casein deficient mice to analyze the function of beta-casein in milk. Beta-casein is not required for essential functions and its composition change does not influence the casein micelle. Beta-casein deficiency has an indirect effect on the growth of the pups.

Research using mice with mutant T-cell antigen receptor (TCR) genes shows that rearrangement or expression of the TCR-beta gene is necessary and sufficient for differentiation of CD4-CD8-thymocytes into the CD4+CD8+ form and for expanding the pool of thymocytes. Expression of the TCR-alpha gene is irrelevant to these processes. Furthermore, the TCR-alpha and TCR-beta mutation does not hinder development of gamma and delta T-cells.

A new mouse model for cystic fibrosis (CF) has been devised that should be useful in trials of potential treatments for this deadly autosomal recessive disorder. The new model was produced through mutagenesis or the genetic disruption of the CF transmembrane conductance regulator gene in murine embryonic stem cells. The detection of the characteristic CF pathophysiology in the mice such as abnormal chloride ion transport verified the similarity of the model to human CF.

Abstract Background Alterations in gene splicing occur in human sporadic colorectal cancer (CRC) and may contribute to tumour progression. The K-ras proto-oncogene encodes two splice variants, K-ras 4A and 4B, and K-ras activating mutations which jointly affect both isoforms are prevalent in CRC. Past studies have established that splicing of both the K-ras oncogene and proto-oncogene is altered in CRC in favour of K-ras 4B. The present study addressed whether the K-Ras 4A proto-oncoprotein can suppress tumour development in the absence of its oncogenic allele, utilising the ApcMin/+ (Min) mouse that spontaneously develops intestinal tumours that do not harbour K-ras activating mutations, and the K-rastmΔ4A/tmΔ4A mouse that can express the K-ras 4B splice variant only. By this means tumorigenesis in the small intestine was compared between ApcMin/+, K-ras+/+ and ApcMin/+, K-rastmΔ4A/tmΔ4A mice that can, and cannot, express the K-ras 4A proto-oncoprotein respectively. Methods The relative levels of expression of the K-ras splice variants in normal small intestine and small intestinal tumours were quantified by real-time RT-qPCR analysis. Inbred (C57BL/6) ApcMin/+, K-ras+/+ and ApcMin/+, K-rastmΔ4A/tmΔ4A mice were generated and the genotypes confirmed by PCR analysis. Survival of stocks was compared by the Mantel-Haenszel test, and tumour number and area compared by Student's t-test in outwardly healthy mice at approximately 106 and 152 days of age. DNA sequencing of codons 12, 13 and 61 was performed to confirm the intestinal tumours did not harbour a K-ras activating mutation. Results The K-ras 4A transcript accounted for about 50% of K-ras expressed in the small intestine of both wild-type and Min mice. Tumours in the small intestine of Min mice showed increased levels of K-ras 4B transcript expression, but no appreciable change in K-ras 4A transcript levels. No K-ras activating mutations were detected in 27 intestinal tumours derived from Min and compound mutant Min mice. K-Ras 4A deficiency did not affect mouse survival, or tumour number, size or histopathology. Conclusion The K-Ras 4A proto-oncoprotein does not exhibit tumour suppressor activity in the small intestine, even though the K-ras 4A/4B ratio is reduced in adenomas lacking K-ras activating mutations.

RB-1, a gene the mutation of which has been linked to retinoblastoma, produces different homozygous and heterozygous effects when inactivated in mouse embryos. Heterozygous mice survive to term and exhibit neither physical abnormalities nor the growth of retinoblastoma tumors. On the other hand, homozygous mouse embryos die before birth and exhibit an array of neural and hematopoietic abnormalities.

Background: Alterations in gene splicing occur in human sporadic colorectal cancer (CRC) and may contribute to tumour progression. The K-ras proto-oncogene encodes two splice variants, Kras 4A and 4B, and K-ras activating mutations which jointly affect both isoforms are prevalent in CRC. Past studies have established that splicing of both the K-ras oncogene and proto-oncogene is altered in CRC in favour of K-ras 4B. The present study addressed whether the K-Ras 4A protooncoprotein can suppress tumour development in the absence of its oncogenic allele, utilising the ApcMin/+ (Min) mouse that spontaneously develops intestinal tumours that do not harbour K-ras activating mutations, and the K-rastmΔ4A/tmΔ4A mouse that can express the K-ras 4B splice variant only. By this means tumorigenesis in the small intestine was compared between ApcMin/+, K-ras+/+ and ApcMin/+, K-rastmΔ4A/tmΔ4A mice that can, and cannot, express the K-ras 4A proto-oncoprotein respectively. Methods: The relative levels of expression of the K-ras splice variants in normal small intestine and small intestinal tumours were quantified by real-time RT-qPCR analysis. Inbred (C57BL/6) ApcMin/+, K-ras+/+ and ApcMin/+, K-rastmΔ4A/tmΔ4A mice were generated and the genotypes confirmed by PCR analysis. Survival of stocks was compared by the Mantel-Haenszel test, and tumour number and area compared by Student's t-test in outwardly healthy mice at approximately 106 and 152 days of age. DNA sequencing of codons 12, 13 and 61 was performed to confirm the intestinal tumours did not harbour a K-ras activating mutation. Results: The K-ras 4A transcript accounted for about 50% of K-ras expressed in the small intestine of both wild-type and Min mice. Tumours in the small intestine of Min mice showed increased levels of K-ras 4B transcript expression, but no appreciable change in K-ras 4A transcript levels. No Kras activating mutations were detected in 27 intestinal tumours derived from Min and compound mutant Min mice. K-Ras 4A deficiency did not affect mouse survival, or tumour number, size or histopathology. Conclusion: The K-Ras 4A proto-oncoprotein does not exhibit tumour suppressor activity in the small intestine, even though the K-ras 4A/4B ratio is reduced in adenomas lacking K-ras activating mutations. [ABSTRACT FROM AUTHOR]

In mammals, the three classical ras genes encode four highly homologous proteins, N-Ras, H-Ras, and the isoforms K-Ras 4A and 4B. Previous studies have shown that K-ras is essential for mouse development and that while K-ras 4A and 4B are expressed during development, K-ras 4A expression is regulated temporally and spatially and occurs in adult kidney, intestine, stomach, and liver. In the present study, the pattern of K-ras 4A expression was examined in a wide range of wild-type adult mouse tissues, and gene targeting was used to generate K-ras 4A-deficient mice to examine its role in development. It was found that K-ras 4A is also expressed in uterus, lung, pancreas, salivary glands, seminal vesicles, bone marrow cells, and cecum, where it was the major K-Ras isoform expressed. Mating between K-ras[sup tmΔ4A/+] mice produced viable K-ras[sup tmΔ4A/tmΔ4A] offspring with the expected Mendelian ratios of inheritance, and these mice expressed the K-ras 4B splice variant only. K-ras[sup tmΔ4A/tmΔ4A] mice were fertile and showed no histopathological abnormalities on inbred (129/Ola) or crossbred (129/Ola × C57BL/6) genetic backgrounds. The results demonstrate that K-Ras 4A, like H- and N-Ras, is dispensable for normal mouse development, at least in the presence of functional K-Ras 4B. [ABSTRACT FROM AUTHOR]

Abstract: Volatile organic compounds (VOCs) exist widely in both the indoor and outdoor environment. The main contributing sources of VOCs are motor vehicle exhaust and solvent utilization. Some VOCs are toxic and carcinogenic to human health, such as benzene. In this study, TiO2–SiO2 based photocatalysts were synthesized using the sol–gel method, with high surface areas of 274.1–421.1m2/g obtained. Two types of pellets were used as catalysts in a fixed-bed reactor installed with a UV black light lamp. Experiments were conducted to compare their efficiencies in degrading the VOCs. Toluene was used as the VOC indicator. When the toluene laden gas stream passed through the photocatalytic reactor, the removal efficiencies were determined using a FTIR multi-gas analyser, which was connected to the outlet of the reactor to analyse the toluene concentrations. As the TiO2–SiO2 pellets used have a high adsorption capacity, they had dual functions as a photocatalyst and adsorbent in the hybrid photocatalysis and adsorption system. The experiments demonstrated that the porous photocatalyst with very high adsorptive capacity enhanced the subsequent photocatalysis reactions and lead to a positive synergistic effect. The catalyst can be self-regenerated by photocatalytic oxidation of the adsorbed VOCs. When the UV irradiation and feeding gas is continuous, a destruction efficiency of about 25% was achieved over a period of 20h. Once the system was designed and operated into adsorption/regeneration mode, a higher removal efficiency of about 55% was maintained. It was found that the catalyst pellets with a higher surface area (421m2/g) achieved higher conversion efficiency (100%) for a longer period than those with a lower surface area. A full spectrum scan was carried out using a Bio-rad Infrared spectrometer, finding that the main components of the treated gas stream leaving the reactor, along with untreated toluene, were CO2 and water. The suspected intermediates of aliphatic hydrocarbons and CO were found in minimal amounts or were non detectable. The kinetic rate constants were calculated from the experimental results, it appeared that the stronger adsorption capacity, i.e. larger specific surface area, the higher conversion efficiency would be achieved. [Copyright &y& Elsevier]