B6.129-Arg1^tm1Rki/J

Stock number: 007741
Research areas: Developmental Biology Research, Internal/Organ Research, Metabolism Research, Neurobiology Research, Reproductive Biology Research, Research Tools

Description

These hepatic arginase (AI)-mutant mice may be useful in studying metabolic defects of arginase I deficiency, urea cycle (excretion of excess nitrogen), and neuronal development and function.

Detailed description

Homozygous AI-mutant mice completely lack hepatic arginase (AI) activity, exhibit hyperagrininemia, severe symptoms of hyperammonemia (ncluding decerebrate posture, lethargy, and high-frequency tremor of the extremities, particularly the tail) and die between 10-14 days after birth. Neural stem cells (NCSs) isolated from homozygous mice exhibit abnormal proliferation and differentiation. In addition, haploid germ cells carrying the disrupted AI allele may be less fit/less effective in forming zygotes compared to wild-type spermatozoa. Heterozygotes are viable and fertile. These AI-mutant mice may be useful in studying metabolic defects of arginase I deficiency, urea cycle (excretion of excess nitrogen), and neuronal development and function.

Development

A targeting vector was designed to replace exon 4 of the targeted gene with a neomycin resistance gene. The construct was electroporated into 129-derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts, and the resulting chimeric males were bred with C57BL/6 females. Mutant mice were reportedly backcrossed to C57BL/6 mice for ten generations prior to sending to The Jackson Laboratory Repository (see SNP notes below). During backcrossing, the Y chromosome may not have been fixed to the C57BL/6J genetic background. Upon arrival, mutant mice were bred to C57BL/6J inbred mice (Stock No. 000664) for one generation to establish the colony. After this, mutant mice were bred with wildtype mice from the colony to maintain the strain.

A 32 SNP (single nucleotide polymorphism) panel analysis, with markers covering all 19 chromosomes and the X chromosome, was performed on the rederived living colony at The Jackson Laboratory Repository. This revealed one marker on chromosome 8 and one marker on chromosome 12 that was not fixed for C57BL/6 allele-type (e.g.: still segregating for 129 allele-type markers). The marker on chromosome 8 may be fixed as homozygous for the 129 allele-type. These data suggest the mice may not have been backcrossed to C57BL/6 for as many generations as originally reported prior to arrival at The Jackson Laboratory Repository.

Allele

Symbol: Arg1^tm1Rki
Name: targeted mutation 1, Ramaswamy K Iyer
MGI accession ID: MGI:2660809
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Arg1
Marker name: arginase, liver
Chromosome: 10
Strain of origin: Not Specified
Molecular note: A neomycin selection cassette replaced a genomic fragment containing exon 4. Activity assays demonstrated that no functional protein was made from this allele.