B6.129S-Nr5a2^tm1Sakl/DjmJ

Stock number: 024054
Research areas: Cardiovascular Research, Cell Biology Research, Developmental Biology Research, Endocrine Deficiency Research, Internal/Organ Research, Metabolism Research, Research Tools

Description

These LRH-1^flox/flox mice possess loxP sites flanking the second zinc finger of the DNA-binding domain of the nuclear receptor subfamily 5, group A, member 2 gene. This strain may be useful for studying the coordinated actions of endocrine signaling.

Detailed description

These LRH-1^flox/flox mutant mice possess loxP sites flanking exon 5, encoding the second zinc finger of the DNA-binding domain of the nuclear receptor subfamily 5, group A, member 2 (Nr5a2) gene. LRH-1 is a transcription factor expressed in liver, pancreas, intestine, and ovary where it regulates cholesterol and bile acid homeostasis, cell proliferation, and steroidogenesis. Homozygous mice are viable and fertile. When bred to mice that express tissue-specific Cre recombinase, resulting offspring will have exon 5 deleted in the cre-expressing tissues.

For example, when bred to B6.Cg-Tg(Alb-cre)21Mgn/J mice (Stock No. 003574) expressing cre in the liver, flox/flox:AlbCre mice contain decreased levels of circulating cholesterol and aspartate transaminase. They have an abnormal composition of bile acid.

Development

A targeting vector was designed to insert a loxP site upstream of exon 5, and a second loxP site followed by a frt-flanked neomycin resistance (neo) cassette downstream of exon 5 of the nuclear receptor subfamily 5, group A, member 2 (Nr5a2) gene. The construct was electroporated into 129S6/SvEvTac-derived embryonic stem (ES) cells, and correctly targeted ES cells were injected into C57BL/6J blastocysts. Offspring were bred with B6.129S4-Gt(ROSA)26Sor^tm1(FLP1)Dym/RainJ transgenic mice (Stock No. 009086) to delete the neo cassette, and progeny were crossed to remove the Flp-expressing transgene. These mice were backcrossed to C57BL/6J mice until they were congenic using JAX Genome Scanning Service. Upon arrival, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.

Allele

Symbol: Nr5a2^tm1Sakl
Name: targeted mutation 1, Steven A Kliewer
MGI accession ID: MGI:3795276
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Synonyms: LRH-1^floxed
Marker symbol: Nr5a2
Marker name: nuclear receptor subfamily 5, group A, member 2
Marker synonyms: B1F; B1F2; CPF; D1Ertd308e; FTF; FTZ-F1; FTZ-F1beta; hB1F-2; LRH1; Lrh-1; UF2-H3B
Chromosome: 1
Strain of origin: 129S/SvEv
Molecular note: An frt-flanked neo cassette with a 5' loxP site was inserted downstream of exon 5 and an additional loxP site was inserted upstream of exon 5. Germ line, flp-mediated recombination was used to remove the neo cassette leaving exon 5 floxed.