B6(129S4)-Snrk^tm1.1Hxu/J

Stock number: 033222
Product name: SNRK^loxp
Research areas: Research Tools

Description

SNRK^loxP conditional knock-out mice possess loxP sites flanking exon 4 of the Snrk gene and may be useful for studying adipose tissue inflammation and energy homeostasis.

Detailed description

Snrk (SNF related kinase) is a member of the sucrose nonfermenting (SNF)-related kinase family of serine/threonine kinases and is abundantly expressed in adipose tissue. It is also expressed in heart, brain, endothelial cells, and cardiomyocytes. Allelic variants of Snrk are associated with obesity risk. Expression of Snrk is decreased in adipose tissue of obese mice. These conditional knock-out mice possess loxP sites flanking exon 4 of the Snrk gene. Mice homozygous for the allele are viable and fertile. When bred to mice that express tissue-specific Cre recombinase, resulting offspring will have exon 4 deleted in cre-expressing tissues creating a null allele. This strain may be useful for studying adipose tissue inflammation and energy homeostasis.

When bred to B6.FVB-Tg(Adipoq-cre)1Evdr/J (Stock No. 028020) with cre expression in adipose tissue, resulting progeny develop inflammation in white adipose tissue, ectopic lipid deposits in liver and muscle, and impaired adaptive thermogenesis in brown adipose tissue.

Development

This tm1c knock-out first mutant strain is derived from a KOMP (Knockout Mouse Project) embryonic stem (ES) cell line. The targeting vector was inserted at position 122156726 of Chromosome 9 upstream of exon 4 (Build GRCm38). The cassette is composed of an FRT site followed by lacZ sequence, a loxP site, neomycin resistance gene under the control of the human beta-actin promoter, SV40 polyA, a second FRT site and a second loxP site. The third loxP site is inserted downstream of exon 4 at position 122157552. Thus, exon 4 is thus flanked by loxP sites. The construct was electroporated into C57BL/6J-derived embryonic stem (ES) cells. The clone was expanded and injected into blastocysts at the Brown University Transgenic Mouse Core. Germ-line transmission was achieved by mating male chimeric founders with C57BL/6J female mice. Offspring, were bred with B6.129S4-Gt(ROSA)26Sor^tm2(FLP*)Sor/J mice to delete the neo/lacZ cassette. The resulting progeny were crossed to remove the transgene. Upon arrival, mice were bred to C57BL/6J for at least 1 generation to establish the colony.

A 48 SNP (single nucleotide polymorphism) panel analysis, with 43 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 mice sent to The Jackson Laboratory Repository (and used to freeze sperm) in 2019. One of the 43 markers, on Chromosome 7, was found to be segregating with 129. Also, the mice we received were heterozygous for the rd8 recessive mutation associated with retinal degeneration on Chromosome 1 within the Crb1 locus. This suggests the C57BL/6 contributions may be a mix of C57BL/6J and C57BL/6N.

Allele

Symbol: Snrk^tm1.1Hxu
Name: targeted mutation 1.1, Haiyan Xu
MGI accession ID: MGI:6279960
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed)
Synonyms: SNRK^loxp
Marker symbol: Snrk
Marker name: SNF related kinase
Marker synonyms: 2010012F07Rik; HSNFRK; MGC:28970; mKIAA0096; SNRK
Chromosome: 9
Strain of origin: C57BL/6
Molecular note: The KOMP targeting vector was inserted at position 122156726 of Chromosome 9 upstream of exon 4 (Build GRCm38). The cassette is composed of an FRT site followed by lacZ sequence, a loxP site, neomycin resistance gene under the control of the human beta-actin promoter, SV40 polyA, a second FRT site and a second loxP site. The third loxP site is inserted downstream of exon 4 at position 122157552. Flp-mediated recombination removed the FRT-flanked lacZ/neo cassette leaving exon 4 floxed.