STOCK Akap12^tm1Ihg/J

Stock number: 026228
Product name: mSSeCKS knock-out
Research areas: Developmental Biology Research, Internal/Organ Research, Reproductive Biology Research

Description

These Akap12 knock-out mice exhibit defective fertility and develop prostate hyperplasia.

Detailed description

The Akap12 gene, also known as SSeCKS, encodes for a scaffold protein that is involved in signal transduction, cell growth and blood–brain barrier regulation. In human prostate cancer, AKAP12 is downregulated. In these knock-out mice, exon 2 of the Akap12 gene has been replaced by a lacZ-NEO cassette. No gene product (protein) is detected by Western blot analysis of testes, bladder, lung, brain, heart, ovary, or prostate tissue from homozygous animals. 3-4% of mice homozygous for the knock-out allele on the B6;129 background die spontaneously as early as 4 months of age, and 10-25% of surviving homozygotes on the B6;129 background are infertile or exhibit delayed fertility (requiring breeding pairs to be housed for up to 3 weeks). Homozygous males on the B6;129 background at 2 months of age exhibit increased prostate gland weight. Homozygotes develop hyperplasia in the anterior and ventral prostate lobes. At one year of age, less than 30% of homozygous males develop prostatic focal dysplasia. Apoptosis in prostate tissue is increased. Histological analysis reveals liver granulomas, larger cell size and vascularization of the lung, and increased germinal center red pulp layer.

Alleles are frequently moved to a genetic background different from that on which an allele was first characterized. This is the case for the strain above. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Development

A targeting vector containing a lacZ-NEO cassette was used to disrupt exon 2 of the targeted gene. The construct was electroporated into 129S4/SvJae derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into 129SvJ blastocysts. The resulting chimeric animals were tested for germline transmission. The mice were then backcrossed onto the C57BL/6 background for 6 generations. During backcrossing, the Y chromosome may not have been fixed to the C57BL/6 genetic background. The mutant mice were then crossed to other mutant lines on various genetic backgrounds, including DBA/2 and FVB. Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the colony.

Allele

Symbol: Akap12^tm1Ihg
Name: targeted mutation 1, Irwin H Gelman
MGI accession ID: MGI:5286076
Generation method: Targeted
Attributes: Null/Knockout
Synonyms: mSSeCKS^-
Marker symbol: Akap12
Marker name: A kinase (PRKA) anchor protein (gravin) 12
Marker synonyms: AKAP12A; AKAP12B; AKAP12G; AKAP250; Srcs5; SSeCKS; Tsga12
Chromosome: 10
Strain of origin: 129S4/SvJae
Molecular note: A lacZ followed by a neomycin selection cassette were inserted in exon2. Western blot analysis demonstrated the absence of all three major isoforms (alpha, beta, gamma).