Distinct downstream targets manifest p53-dependent pathologies in mice.

ABSTRACT: Mdm2, the principal negative regulator of p53, is critical for survival, a fact clearly demonstrated by the p53-dependent death of germline or conditional mice following deletion of Mdm2. On the other hand, Mdm2 hypomorphic (Mdm2^Puro/Δ7-12) or heterozygous (Mdm2^+/-) mice that express either 30 or 50% of normal Mdm2 levels, respectively, are viable but present distinct phenotypes because of increased p53 activity. Mdm2 levels are also transcriptionally regulated by p53. We evaluated the significance of this reciprocal relationship in a new hypomorphic mouse model inheriting an aberrant Mdm2 allele with insertion of the neomycin cassette and deletion of 184-bp sequence in intron 3. These mice also carry mutations in the Mdm2 P2-promoter and thus express suboptimal level

SUBMITTER: Pant V 

PROVIDER: S-EPMC5106874 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature