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Targeted Genomic Disruption of H-ras and N-ras, Individually or in Combination, Reveals the Dispensability of Both Loci for Mouse Growth and Development

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dc.creator Esteban, Luis Miguel
dc.creator Vicario-Abejón, Carlos
dc.creator Swaminathan, Nalini
dc.creator Fernández-Medarde, Alberto
dc.date 2008-06-17T12:00:49Z
dc.date 2008-06-17T12:00:49Z
dc.date 2001-03
dc.date.accessioned 2017-01-31T01:42:41Z
dc.date.available 2017-01-31T01:42:41Z
dc.identifier Molecular and Cellular Biology 21(5): 1444–1452 (2001)
dc.identifier 1098-5549
dc.identifier http://hdl.handle.net/10261/5141
dc.identifier 10.1128/MCB.21.5.1444-1452.2001
dc.identifier.uri http://dspace.mediu.edu.my:8181/xmlui/handle/10261/5141
dc.description et al.
dc.description Mammalian cells harbor three highly homologous and widely expressed members of the ras family (H-ras, N-ras, and K-ras), but it remains unclear whether they play specific or overlapping cellular roles. To gain insight into such functional roles, here we generated and analyzed H-ras null mutant mice, which were then also bred with N-ras knockout animals to ascertain the viability and properties of potential double null mutations in both loci. Mating among heterozygous H-ras+/− mice produced H-ras−/− offspring with a normal Mendelian pattern of inheritance, indicating that the loss of H-ras did not interfere with embryonic and fetal viability in the uterus. Homozygous mutant H-ras−/− mice reached sexual maturity at the same age as their littermates, and both males and females were fertile. Characterization of lymphocyte subsets in the spleen and thymus showed no significant differences between wild-type and H-ras−/− mice. Analysis of neuronal markers in the brains of knockout and wild-type H-ras mice showed that disruption of this locus did not impair or alter neuronal development. Breeding between our H-ras mutant animals and previously available N-ras null mutants gave rise to viable double knockout (H-ras−/−/N-ras−/−) offspring expressing only K-ras genes which grew normally, were fertile, and did not show any obvious phenotype. Interestingly, however, lower-than-expected numbers of adult, double knockout animals were consistently obtained in Mendelian crosses between heterozygous N-ras/H-ras mice. Our results indicate that, as for N-ras, H-ras gene function is dispensable for normal mouse development, growth, fertility, and neuronal development. Additionally, of the three ras genes, K-ras appears to be not only essential but also sufficient for normal mouse development.
dc.description This work was supported by FEDER grant 1FD1997-1735 from Ministerio de Ciencia y Tecnología, Spain.
dc.description Peer reviewed
dc.format 25093 bytes
dc.format application/pdf
dc.language eng
dc.publisher American Society for Microbiology
dc.relation http://dx.doi.org/10.1128/MCB.21.5.1444-1452.2001
dc.rights closedAccess
dc.title Targeted Genomic Disruption of H-ras and N-ras, Individually or in Combination, Reveals the Dispensability of Both Loci for Mouse Growth and Development
dc.type Artículo


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