While K-ras is essential for mouse development, expression of the K-ras 4A splice variant is dispensable

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. and 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, 23 24: 9245-9250. doi:10.1128/MCB.23.24.9245-9250.2003

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Author 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.
Title While K-ras is essential for mouse development, expression of the K-ras 4A splice variant is dispensable
Journal name Molecular And Cellular Biology   Check publisher's open access policy
ISSN 0270-7306
1098-5549
Publication date 2003-12-01
Sub-type Article (original research)
DOI 10.1128/MCB.23.24.9245-9250.2003
Open Access Status File (Publisher version)
Volume 23
Issue 24
Start page 9245
End page 9250
Total pages 6
Place of publication Washington, DC, United States
Publisher American Society for Microbiology
Language eng
Abstract 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(tm-Delta4A/t-Delta4A) 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.
Keyword Biochemistry & Molecular Biology
Cell Biology
N-ras
H-ras
Plasma-membrane
Activate Raf-1
Gene
Isoforms
Carcinogenesis
Transformation
Combination
Oncogene
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
Institute for Molecular Bioscience - Publications
 
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Created: Sat, 26 Jan 2008, 02:04:10 EST