B6.129S6-Nr1h2^tm1Djm/J

Stock number: 014633
Product name: LXRβ- (Δexons5-6) on C57BL/6
Research areas: Cardiovascular Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Metabolism Research, Reproductive Biology Research

Description

In this knockout strain a neomycin resistance cassette replaces exons 5-6 of the (Nr1h2) gene abolishing gene function. These mice may be useful for studying lipid and cholesterol metabolism, and regulation of the immune response.

Detailed description

In this strain a neomycin (neo) resistance cassette replaces exons 5-6 of the nuclear receptor subfamily 1, group H, member 2 (Nr1h2) gene, abolishing gene function. Homozygotes are viable, fertile, and normal in size. Also known as liver X receptor beta (Lxrβ), Nr1h2 binds to retinoid X receptors (RXRα, RXRβ, RXRγ; NR2B1, NR2B2, and NR2B3) and is activated by oxysterols to regulate the expression of genes involved in cholesterol metabolism. Homozygous Lxrβ^-/- mice lose their ability to appropriately regulate cholesterol, lipid, and carbohydrate metabolism, and have defects in immune function. These defects are more severe when combined with the knockout of Lxrα (available as Stock No. 013761). These mice may be useful for studying lipid and cholesterol metabolism, and regulation of the immune response.

Development

A targeting vector was designed to replace exons 5-6 encoding DNA-binding domain and the ligand-binding domains of the nuclear receptor subfamily 1, group H, member 2 (Nr1h2) gene with a neomycin resistance (neo) cassette. The construct was electroporated into 129S6/SvEvTac-derived SM1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and the resulting chimeric mice were bred to C57BL/6 mice. The donating investigator reported that these mice were backcrossed at least 10 generations to a C57BL/6 background (see SNP note below). Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation to establish the colony.

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 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 rederived living colony at The Jackson Laboratory Repository. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, 1 of 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed C57BL/6J ; C57BL/6N genetic background.

Allele

Symbol: Nr1h2^tm1Djm
Name: targeted mutation 1, David J Mangelsdorf
MGI accession ID: MGI:3041856
Generation method: Targeted
Attributes: Null/Knockout
Synonyms: LXRbeta^-
Marker symbol: Nr1h2
Marker name: nuclear receptor subfamily 1, group H, member 2
Marker synonyms: LXR beta; LXRB; LXR-b; LXRbeta; NER; NER-I; OR-1; RIP15; UNR; Unr2
Chromosome: 7
Strain of origin: 129S6/SvEvTac
Molecular note: Insertion of a targeting vector replaced exons 5 and 6 with a neomycin resistance cassette creating a null allele. Exons 5 and 6 encode the DNA-binding and ligand-binding domains.