C57BL/6-Ass1^{tm1c(EUCOMM)Hmgu}/VantJ

Stock number: 037821
Product name: ASS1^F
Research areas: Cancer Research, Internal/Organ Research, Metabolism Research, Research Tools

Description

Ass1^F mice possess loxP sites flanking exon 8 of the argininosuccinate synthetase 1 (Ass1) gene. These mice may be useful for studying arginosuccinate synthetase deficiency in cre-expressing tissues.

Detailed description

Argininosuccinate synthetase 1 (ASS1) is an enzyme that catalyzes the synthesis of argininosuccinate from citrulline and aspartate in the urea cycle. Mutations in Ass1 have been implicated in the rare inborn metabolism disease, citrullinemia. ASS1 deficiency results in excessive amounts of ammonia in the blood and tissues. Common symptoms in human patients include lack of appetite, seizures, intolerance to protein, hepatomegaly, and/or coma. Mice that are homozygous for this floxed allele are viable and fertile. When bred to mice that express tissue-specific Cre recombinase, resulting offspring will have exon 8 deleted in the cre-expressing tissues. These Ass1^F mice may be useful for studying citrullinemia.

Development

C57BL/6N-derived JM8A3.N1 embryonic stem (ES) cells (clone HEPD0731_5_F08) bearing the Ass1^{tm1a(EUCOMM)Hmgu} targeted allele were obtained from The European Conditional Mouse Mutagenesis Program (EUCOMM). The targeting cassette is composed of an FRT site followed by lacZ sequence and an initial loxP site upstream of exon 8 of the argininosuccinate synthetase 1 (Ass1) gene. This first loxP site is followed by a neomycin resistance gene under the control of the human beta-actin promoter, SV40 polyA, a second FRT site and a second loxP site. A third loxP site is inserted downstream of exon 8. Targeted ES cells were injected into recipient blastocysts. The resulting chimeric mice were bred with mice expressing Flp recombinase, on a C57BL/6 background (Riken BioResource Center), to excise the FRT site flanked lacZ-loxP-neo cassette. Progeny were crossed to C57BL/6 mice to remove the Flp-expressing transgene. The resulting heterozygous Ass1^F mice, with neo cassette removed and floxed exon 8 intact, were maintained on a C57BL/6 background by the donating laboratory. Upon arrival at The Jackson Laboratory, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes (Stock No. 000664).

Allele

Symbol: Ass1^{tm1c(EUCOMM)Hmgu}
Name: targeted mutation 1c, Helmholtz Zentrum Muenchen GmbH
MGI accession ID: MGI:7441939
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed)
Marker symbol: Ass1
Marker name: argininosuccinate synthetase 1
Marker synonyms: ASS; Ass-1; ASSA; CTLN1; fold
Chromosome: 2
Strain of origin: C57BL/6N-A^tm1Brd
Molecular note: The targeting cassette is composed of an FRT site followed by lacZ sequence and an initial loxP site upstream of exon 8. This first loxP site is followed by a neomycin resistance gene under the control of the human beta-actin promoter, SV40 polyA, a second FRT site and a second loxP site. A third loxP site is inserted downstream of exon 8. Flp-mediated recombination removed the lacZ and neo cassette.