B6;129-Nr4a3^tm1Omc/J

Stock number: 033762
Product name:  nor-1, NOR1 KO
Research areas: Cancer Research, Developmental Biology Research, Immunology, Inflammation and Autoimmunity Research, Neurobiology Research, Research Tools

Description

Nor1 (Nr4a3) beta-galactosidase knock-in/knock-out mice exhibit increased susceptibility to induced seizures, behavioral and neurodevelopmental defects. They may be useful in studies of inflammation, cancer and neurodevelopment.

Detailed description

This NOR1 knock-out allele consists of a lacZ gene and NEO cassette in place of exon 2, which encodes amino acids 212 to 231, upstream of the DNA binding domain. The targeted Nr4a3 gene encodes a nuclear hormone receptor involved in brain development, regulation of inflammation, and cell proliferation. Chromosomal translocation mutations in this gene have been associated with Extraskeletal Myxoid Chondrosarcoma and Epithelial-Myoepithelial Carcinoma. In heterozygous mice, beta-galactosidase staining mimics the endogenous Nr4a3 expression pattern. Heterozygotes are viable and fertile. Homozygotes on a mixed B6;129 background exhibit hyperactivity, bidirectional circling behavior, increased susceptibility to kainic acid-induced limbic seizures, tonic-clonic seizures, as well as abnormal hippocampal development. No mRNA is detected in bone marrow derived macrophages by real-time RT-PCR.

Of note, in the live colony at The Jackson Laboratory, homozygotes exhibit hyperactivity (as above), homozygous females appear to be good mothers and breeding homozygotes together is productive [June 2020].

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. This is the case for the strain above. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Development

A targeting vector containing IRES, a lacZ (beta-galactosidase) gene, and an Mc-1 neomycin resistance cassette was used to disrupt exon 2 (encoding amino acids 212 to 231). The construct was electroporated into unspecified 129/SvEv derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were tested for germline transmission. The donating investigator reports mice were then backcrossed to C57BL/6 for 10 generations and maintained as heterozygotes (see SNP results below). At some point, these mice were bred to Nr4a1^tm1Jmi mice (see Stock No. 006187). Embryos were cryopreserved and then sent to The Jackson Laboratory in 2019. To establish our live colony, an aliquot of frozen embryos was cryorecovered and the Nr4a1^tm1Jmi was removed.

In 2019, 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 first generation rederived living mice at The Jackson Laboratory. This revealed a total of 11 markers that were not fixed for C57BL/6 allele-type. Furthermore, all 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating in some mice. These data suggest that the embryos sent to The Jackson Laboratory Repository were from mice incompletely backcrossed onto C57BL/6, and the C57BL/6 genetic background contributions are a mix of C57BL/6J;C57BL/6N.

Allele

Symbol: Nr4a3^tm1Omc
Name: targeted mutation 1, Orla M Conneely
MGI accession ID: MGI:3037444
Generation method: Targeted
Attributes: Reporter; Null/Knockout
Synonyms: nor-1^-
Marker symbol: Nr4a3
Marker name: nuclear receptor subfamily 4, group A, member 3
Marker synonyms: CHN; CSMF; MINOR; Nor1; NOR-1; NOR-2; TEC
Chromosome: 4
Strain of origin: 129S/SvEv
Molecular note: A lacZ gene and neomycin selection cassette were inserted into exon 2. Beta-galactosidase was expressed from this allele in a pattern similar to the endogenous gene.