STOCK Ncor1^tm1Anh/J

Stock number: 017632
Research areas: Cell Biology Research, Endocrine Deficiency Research, Internal/Organ Research, Mouse/Human Gene Homologs, Research Tools

Description

These NCoR^lox mutant mice possess loxP sites flanking exons 37-40 of the nuclear receptor co-repressor 1 (Ncor1) gene. This strain may be useful for studying the role of NCOR1 on regulation of nuclear receptor signaling.

Detailed description

These NCoR^lox mutant mice possess loxP sites flanking exons 37-40 of the nuclear receptor co-repressor 1 (Ncor1) gene. Exons 37-40 encode two of three 5' receptor interacting domains (RIDs). NCOR1 is recruited through interactions of its RIDs to nuclear receptors, such as retinoic-acid and thyroid-hormone receptors (TR), where it acts as a transcription repressor. Mice that are homozygous for this allele are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. When bred to mice that express tissue-specific Cre recombinase, resulting offspring will have exons 37-40 deleted in the cre-expressing tissues. For example, when bred to B6.Cg-Tg(Alb-cre)21Mgn/J mice (Stock No. 003574) deletion of the two most 5' RIDs (N2 and N3) in the liver results in the inability of NCOR1 to bind to the TR. This strain may be useful for studying the role of NCOR1 on regulation of nuclear receptor signaling.

Development

A targeting vector was designed to insert a loxP site upstream of exon 37 followed by a second loxP site and a frt-flanked neomycin resistance (neo) cassette downstream of exon 40 of the nuclear receptor co-repressor 1 (Ncor1) gene. The construct was electroporated into 129S4/SvJae-derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts and resulting chimeric males were bred to C57BL/6NTac females. The resulting offspring were bred with 129S4-Gt(ROSA)26Sor^tm1(FLP1)Dym/J mice (Stock No. 003946) to delete the neo cassette, and progeny were crossed to remove the Flp-expressing transgene. The mice were subsequently bred to B6.Cg-Tg(Alb-cre)21Mgn/J mice (Stock No. 003574) and B6.Cg-Tg(UBC-cre/ERT2)1Ejb/J mice (Stock No. 008085) for experimental purposes. The DI reports that the Cre-expressing transgene has been removed. These mice were maintained on a mixed background. Upon arrival, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation.

Allele

Symbol: Ncor1^tm1Anh
Name: targeted mutation 1, Anthony N Hollenberg
MGI accession ID: MGI:3821874
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Marker symbol: Ncor1
Marker name: nuclear receptor co-repressor 1
Chromosome: 11
Strain of origin: 129S4/SvJae
Molecular note: A loxP site was inserted upstream of exon 38 and an frt flanked neo cassette with a 5' loxP site was inserted downstream of exon 41. Germ line, flp-mediated recombination was used to remove the neo cassette leaving exons 38 through 41 floxed. These exons encode two of the three receptor interacting domains (N2 and N3).