These Crhr1 knock-out mice exhibit very low plasma corticosterone levels, reduced anxiety response behavior, and have impaired spatial recognition memory. Recent studies suggest that Crhr1 is a critical modulator of mast cell degranulation and stress-induced pathophysiology, including allergy/anaphylaxis, asthma, and irritable bowel syndrome.
Kuo-Fen Lee, The Salk Institute
These mice carry a targeted knock-out of the Crhr1 (corticotropin releasing hormone receptor 1) gene. No mRNA is detected in the cerebellum tissue of homozygotes, and no receptor function is seen in cultured pituitary cells. Pups from homozygote crosses die within 48 hours after birth from lung dysplasia due to insufficient maternal glucocorticoid during fetal development. When corticosterone is administered by drinking water or in utero to homozygous females from embryonic day 12 through postnatal day 14, offspring have normal lung maturation. There is a reported 15% mortality in male mutant mice between 3 -12 weeks of age.
Mutants have very low plasma corticosterone levels, without a diurnal rise. Histological analysis reveals a reduced zona fasciculata layer of the adrenal gland in mature animals. Homozygous mice display reduced anxiety response behavior. Hormonal response to stress, as measured by circulating ACTH and corticosterone, is diminished in homozygous mice due to impairment of the hypothalamic-pituitary-adrenal axis. Female mutants react to stress with slightly higher levels of plasma corticosterone than male mutants.
Induced local inflammation produces slightly higher ACTH plasma levels and 10-fold higher IL-6 plasma levels when compared to wildtype. Swelling is diminished at the treatment site, however.
Recent studies suggest that Crhr1 is a critical modulator of mast cell degranulation and stress-induced pathophysiology, including allergy/anaphylaxis, asthma, and irritable bowel syndrome.
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt exons 5 to 8, which encodes the last 12 amino acids of the first extracellular domain to the fourth transmembrane domain. The construct was electroporated into 129S4/SvJae-derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were backcrossed to C57BL/6 mice. Black and agouti coat colors can be expected from this B6;129 mixed background strain.
|Allele Name||targeted mutation 1, Kuo-Fen Lee|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||CRF1-; CRF-R1-; CRFR1 -; CRHtklee|
|Gene Symbol and Name||Crhr1, corticotropin releasing hormone receptor 1|
|Strain of Origin||129S4/SvJae|
|Molecular Note||A neomycin selection cassette replaced a genomic fragment containing exons 5-8, which encode part of the first transmembrane domain through the fourth transmembrane domain.|
|Mutations Made By|| |
Kuo-Fen Lee, The Salk Institute
Heterozygotes are viable and fertile. Offspring of homozygous females die within 48 hours of birth due to lung dysplasia.
When using the CRFR1 KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #004454 in your Materials and Methods section.