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.
Stephen Cederbaum, University of California Los Angeles
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.
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 Name||targeted mutation 1, Ramaswamy K Iyer|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||AI -|
|Gene Symbol and Name||Arg1, arginase, liver|
|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.|
|Mutations Made By|| |
Ramaswamy Iyer, University of California, Los Angeles
When maintaining a live colony, heterozygous mice may be bred together, to wildtype siblings, or to C57BL/6J inbred mice. Homozygous mice die between 10-14 days after birth.
When using the B6.129-Arg1tm1Rki/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #007741 in your Materials and Methods section.
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