While K-ras is essential for mouse development, expression of the K-ras 4A splice variant is dispensable
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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(tmDelta4A/+) mice produced viable K-ras(tmDelta4A/tmDelta4A) offspring with the expected Mendelian ratios of inheritance, and these mice expressed the K-ras 4B splice variant only. K-ras(tmDelta4A/tmDelta4A) mice were fertile and showed no histopathological abnormalities on inbred (129/Ola) or crossbred (129/Ola x 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.
Plowman , S J , Williamson , D J , O'Sullivan , M J , Doig , J , Ritchie , A-M , Harrison , D J , Melton , D W , Arends , M J , Hooper , M L & Patek , C E 2003 , ' While K-ras is essential for mouse development, expression of the K-ras 4A splice variant is dispensable ' Molecular and Cellular Biology , vol 23 , no. 24 , pp. 9245-9250 . DOI: 10.1128/MCB.23.24.9245-9250.2003
Molecular and Cellular Biology
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