B6.129S2-Pak4^tm1Amin/J

Stock number: 015829
Research areas: Cardiovascular Research, Cell Biology Research, Developmental Biology Research, Neurobiology Research

Description

These Pak4 knock out mice may be useful for studying the role of Pak4 in embryonic and neuronal development.

Detailed description

In this strain, a neo cassette replaces exon 1 of the p21 protein (Cdc42/Rac)-activated kinase 4 (Pak4) gene, abolishing gene expression. Heterozygotes are viable, fertile, normal in size, and do not display any gross physical abnormalities. Homozygotes die by E11.5 due to fetal heart defects. Pak4 is a member of the group B family of PAK serine/threonine kinases and is expressed early in development in a variety of tissues. It is involved in the formation of filopodia in response to Cdc42, promoting neuronal growth. Improper folding of the caudal neural tubes of homozygous embryos results in the formation of two neural lumens. They also exhibit abnormalities in the development, migration and differentiation of neurons. Specifically, axonal outgrowth was impaired, and neurons failed to migrate to their proper locations. These mice may be useful for studying the role of Pak4 in embryonic and neuronal development.

Development

A targeting vector was designed to replace exon 1 encoding the p21 protein (Cdc42/Rac)-activated kinase 4 (Pak4) gene with a neomycin resistance (neo) cassette. The construct was electroporated into 129S2/SvPas-derived D3 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts and the resulting chimeric males were bred to C57BL/6J females. The donating investigator reported that these mice were then backcrossed to C57BL/6J mice for at least 9 generations to maintain the colony (see SNP note below). Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation 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, 3 of 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 mixed C57BL/6J ; C57BL/6N genetic background.

Allele

Symbol: Pak4^tm1Amin
Name: targeted mutation 1, Audrey Minden
MGI accession ID: MGI:2679635
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Pak4
Marker name: p21 (RAC1) activated kinase 4
Chromosome: 7
Strain of origin: 129
Molecular note: Exon 1, containing the initiating methionine and the critical GTPase-binding domaain, was replaced with a PGK-neo cassette inserted by homologous recombination. Neither transcript nor protein was detected by Northern and Western blot analysis of homozygous mutant brain tissue.
General note: ES cell line = D3 or E14.