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PMID: 9334313 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

K-ras is an essential gene in the mouse with partial functional overlap with N-ras.

Genes & development ·Vol. 11 ·No. 19 ·1997-10-01 ·Pages 2468-81

Johnson L, Greenbaum D, Cichowski K, Mercer K, Murphy E, Schmitt E, Bronson RT, Umanoff H, Edelmann W, Kucherlapati R, Jacks T

Abstract

Mammalian ras genes are thought to be critical in the regulation of cellular proliferation and differentiation and are mutated in approximately 30% of all human tumors. However, N-ras and H-ras are nonessential for mouse development. To characterize the normal role of K-ras in growth and development, we have mutated it by gene targeting in the mouse. On an inbred genetic background, embryos homozygous for this mutation die between 12 and 14 days of gestation, with fetal liver defects and evidence of anemia. Thus, K-ras is the only member of the ras gene family essential for mouse embryogenesis. We have also investigated the effect of multiple mutations within the ras gene family. Most animals lacking N-ras function and heterozygous for the K-ras mutation exhibit abnormal hematopoietic development and die between days 10 and 12 of embryogenesis. Thus, partial functional overlap appears to occur within the ras gene family, but K-ras provides a unique and essential function.

MeSH Terms
Anemia/embryology,genetics Animals Cells, Cultured Chimera/genetics Embryonic and Fetal Development/genetics Female Gene Expression Regulation, Developmental Gene Targeting Genes, ras/genetics Hematopoiesis/genetics Liver/embryology,pathology Male Mice Mice, Inbred C57BL Mice, Knockout Neoplasms/genetics,therapy Phenotype Stem Cells/cytology
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Johnson L
Department of Biology, Massachusetts Institute of Technology, Cambridge 02139, USA.
Greenbaum D
Cichowski K
Mercer K
Murphy E
Schmitt E
Bronson R T
Umanoff H
Edelmann W
Kucherlapati R
Jacks T
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.11.19.2468
Published
1997-10-01
Pages
2468-81
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC316567
Subset
IM
Corrections
ErratumIn
-
External Links
PubMed source DOI: 10.1101/gad.11.19.2468 PMC Full Text View journal details
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