B6.129P2(Cg)-Cdc14b^tm1.2Pzg/J

Stock number: 016896
Research areas: Cancer Research, Cell Biology Research, Sensorineural Research

Description

These Cdc14b^deltaE2 mutant mice are deficient in Cdc14b and exhibit premature aging and impaired DNA damage repair.

Detailed description

Cdc14b encodes a nuclear phosphatase that has been implicated in nuclear organization, centriole duplication, mitotic exit, cell cycle regulation, and DNA damage repair. Mice that are homozygous for this targeted mutation allele are viable, fertile, and normal in size. Truncated gene product (mRNA), that is not expected to produce functional protein, is detected by RT-PCR analysis of MEFs from homozygotes. Homozygotes develop cataracts and kyphosis much earlier than wildtype controls and exhibit impaired contextual fear conditioning. Homozygous females exhibit impaired fertility, with smaller litter sizes than wildtype controls. MEFs isolated from homozygotes display defective DNA damage repair and slowed growth rate in later-passages.

Development

A FRT site flanked targeting vector containing Kan/Neo selection cassette with an upstream loxP site was utilized in the construction of this mutant. This selection cassette was inserted upstream of exon 2 of the targeted gene, and another loxP site was inserted downstream of exon 2. This construct was electroporated into 129P2/OlaHsd-derived E14Tg2a.4embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. The resulting chimeric animals were crossed to Meox2-Cre mice to excise exon 2. The donating investigator reported that mice were backcrossed to C57BL/6 mice for 7 generations (see SNP note below). Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the colony.

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, all 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a C57BL/6N genetic background.

Allele

Symbol: Cdc14b^tm1.2Pzg
Name: targeted mutation 1.2, Pumin Zhang
MGI accession ID: MGI:4948253
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Cdc14b
Marker name: CDC14 cell division cycle 14B
Chromosome: 13
Strain of origin: 129P2/OlaHsd
Molecular note: Cre-mediated recombination removed exon 2 and the neo cassette. RT-PCR confirmed the expression of two truncated transcripts that are not predicted to produce a functional protein.