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PMID:12917627

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Citation

Martín, J, Hunt, SL, Dubus, P, Sotillo, R, Néhmé-Pélluard, F, Magnuson, MA, Parlow, AF, Malumbres, M, Ortega, S and Barbacid, M (2003) Genetic rescue of Cdk4 null mice restores pancreatic beta-cell proliferation but not homeostatic cell number. Oncogene 22:5261-9

Abstract

Lack of Cdk4 expression in mice leads to insulin-deficient diabetes and female infertility owing to a reduced number of pancreatic beta cells and prolactin-producing pituitary lactotrophs, respectively. Cdk4 null mice display also reduced body and organ size. Here, we show that Cdk4 is essential for the postnatal proliferation of pancreatic beta cells but not for embryonic neogenesis from ductal epithelial cells. Re-expression of endogenous Cdk4 in beta cells and in the pituitary gland of Cdk4 null mice restores cell proliferation and results in fertile and normoglycemic animals, thus, demonstrating that the proliferation defects in these cellular populations are cell autonomous because of the lack of Cdk4 expression. However, these mice remain small in size, indicating that this phenotype is not because of pancreatic- or pituitary-mediated endocrine defects. This phenotype is a consequence of reduced cell numbers rather than reduced cell size. Thus, mammalian Cdk4 is not only involved in controlling proliferation of specific cell types but may play a wider role in establishing homeostatic cell numbers.

Links

PubMed Online version:10.1038/sj.onc.1206506

Keywords

Animals; Body Constitution/genetics; Cell Division/genetics; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinases/biosynthesis; Cyclin-Dependent Kinases/genetics; Cyclin-Dependent Kinases/metabolism; Islets of Langerhans/metabolism; Mice; Mutation; Phenotype; Proto-Oncogene Proteins

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:CDK4

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:CDK4

acts_upstream_of_or_within

GO:0042127: regulation of cell population proliferation

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2154520
MGI:MGI:2154521

P

Seeded From UniProt

complete


See also

References

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