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Loss of Cdk4 expression causes insulin-deficient diabetes and Cdk4 activation results in beta-islet cell hyperplasia.

Abstract：

:To ascertain the role of cyclin-dependent kinase 4 (Cdk4) in vivo, we have targeted the mouse Cdk4 locus by homologous recombination to generate two strains of mice, one that lacks Cdk4 expression and one that expresses a Cdk4 molecule with an activating mutation. Embryonic fibroblasts proliferate normally in the absence of Cdk4 but have a delayed S phase on re-entry into the cell cycle. Moreover, mice devoid of Cdk4 are viable, but small in size and infertile. These mice also develop insulin-deficient diabetes due to a reduction in beta-islet pancreatic cells. In contrast, mice expressing a mutant Cdk4 that cannot bind the cell-cycle inhibitor P16INK4a display pancreatic hyperplasia due to abnormal proliferation of beta-islet cells. These results establish Cdk4 as an essential regulator of specific cell types.

journal_name

Nat Genet

journal_title

Nature genetics

authors

Rane SG,Dubus P,Mettus RV,Galbreath EJ,Boden G,Reddy EP,Barbacid M

doi

10.1038/8751

keywords:

subject

Has Abstract

pub_date

1999-05-01 00:00:00

pages

44-52

issue

1

eissn

1061-4036

issn

1546-1718

journal_volume

22

pub_type

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