B6N;129-Egr1^tm1Jmi/J

Stock number: 012924
Product name: NGFI-A
Strain synonyms: Egr1 KO
Research areas: Cardiovascular Research, Endocrine Deficiency Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research

Description

These Egr1 knock-out mice may be useful for studying carcinogenesis, inflammation, atherosclerosis, scleroderma, ischemic injury, tissue repair, fibrosis, matrix remodeling and wound healing.

Detailed description

In this strain a coding exon upstream of the DNA-binding domain of the early growth response 1 (Egr1) gene is replaced with a neo cassette, abolishing gene function. Homozygous Egr1^-/- mice are viable and normal in size. Homozygous females are sterile, are absent of corpora lutea, and display a 30% reduction in the weight of the uterus. These mice exhibit an impaired inflammatory response, impaired wound healing, and attenuated dermal fibrosis after TGF-β or bleomycin stimulation. Macrophages from Egr1^-/- mice showed reduced TNF-α secretion when stimulated with TGF-β. These mice may be useful for studying carcinogenesis, inflammation, atherosclerosis, scleroderma, ischemic injury, tissue repair, fibrosis, matrix remodeling and wound healing.

Development

A targeting vector was designed to place a neomycin resistance (neo) cassette into a coding exon upstream of the DNA-binding domain of the early growth response 1 (Egr1) gene. The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-Kitl⁺-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts and the resulting chimeric males were bred to C57BL/6NTac females to generate a colony of Egr1^-/- mice. The Donating investigator confirms that these mice were backcrossed to C57BL/6NTac mice for 26 generations (see SNP note below). Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6NJ (Stock No. 005304) 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. 4 markers on 3 chromosomes, 6, 12, and 13, were found to be segregating, suggesting an incomplete backcross.

Allele

Symbol: Egr1^tm1Jmi
Name: targeted mutation 1, Jeffrey Milbrandt
MGI accession ID: MGI:2384433
Generation method: Targeted
Attributes: Null/Knockout
Synonyms: egr-1-; Egr1^-; Egr-1⁰; Egr-1^ko; NGFI-A^-
Marker symbol: Egr1
Marker name: early growth response 1
Marker synonyms: A530045N19Rik; AT225; Egr-1; ETR103; G0S30; Krox-1; Krox24; KROX-24; Ngf1; NGF1-A; Ngfi; NGFIA; NGFI-A; TIS8; Zenk; Zfp-6; Zif268; ZIF-268; ZNF225
Chromosome: 18
Strain of origin: 129
Molecular note: The gene was disrupted by insertion of a PGK-neo cassette into a coding exon upstream of the DNA-binding domain via homologous recombination. The targeted mutation introduces several stop codons resulting protein truncation upstream of the DNA-binding domain. Gene expression and protein product were not observed in homozygous mutant ES cells.
General note: ES cell line = AB1 (129S7/SvEvBrd-Hprt⁺) or D3 (129S2/SvPas).