B6.129S4(Cg)-Crh^tm2.1Maj/J

Stock number: 030110
Product name: Crhflox
Research areas: Endocrine Deficiency Research, Neurobiology Research, Research Tools

Description

The coding region (exon 2) of the mouse Crh gene is flanked by loxP sites in this conditional targeted mutation. Cre-mediated excision of the floxed region can direct tissue-specific knockouts of the gene, useful in studies of anxiety-like behaviors and endocrine function.

Detailed description

Stress-stimulated corticotropin-releasing hormone (CRH) release is essential for coordinating the neuroendocrine and behavioral responses to stress. Stress, and stress-associated dysfunction of CRH neuronal circuitries and the hypothalamic-pituitary-adrenal (HPA) axis in particular, have been implicated in the onset and maintenance of specific psychiatric disorders such as major depression and anxiety disorders. CRH is the major hypothalamic regulator of ACTH release and adrenal glucocorticoid secretion.

Exon 2 of the mouse Crh (corticotropin releasing hormone) gene is flanked by loxP sites in this conditional mutant allele. Cre-mediated excision of the floxed region results in a knockout allele.

Floxed and wildtype mice have a similar CRH expression pattern and comparable CRH fluorescent density, indicating that the insertion of loxP sites does not affect protein expression. Homozygous floxed mice have normal food intake and body weight, and show morning and evening plasma corticosterone levels comparable to those of wildtype mice.

Hypothalamus-specific Crh knockout mice, created by crossing these Crh floxed mice with Sim1-cre mice (see Stock No. 006451), exhibit adrenal atrophy as well as decreased basal, diurnal and stressor-stimulated plasma corticosterone secretion and basal plasma adrenocorticotropic hormone. The compound mutant mice have a profound anxiolytic phenotype when evaluated using multiple stressors including open-field, elevated plus maze, holeboard, light–dark box and novel object recognition task.

Development

A loxP site was introduced to intron 1 and a FRT-flanked neomycin cassette followed by a loxP site was placed in intron 2 via homologous recombination in 129S4/SvJae-derived J1 embryonic stem (ES) cells. Resultant chimeric animals were bred to animals expressing Flp recombinase to excise the neomycin cassette, leaving exon 2, encoding the entire coding region, flanked by loxP sites. This line was backcrossed to C57BL/6J for 10 generations by the donating laboratory.

Allele

Symbol: Crh^tm2.1Maj
Name: targeted mutation 2.1, Joseph Majzoub
MGI accession ID: MGI:5819101
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Synonyms: Crh flox
Marker symbol: Crh
Marker name: corticotropin releasing hormone
Marker synonyms: corticotropin releasing factor; corticotropin-releasing factor; CRF; CRH1; LOC383938
Chromosome: 3
Strain of origin: 129S4/SvJae
Molecular note: A loxP site was introduced to intron 1 and a FRT-flanked neomycin cassette followed by a loxP site was placed in intron 2. Flp-mediated recombination removed the FRT-flanked neo cassette leaving exon 2 floxed.