B6.129S4-Ucn^tm1Abas/J

Stock number: 020103

Description

These Ucn (urocortin) knockout mice exhibit an altered corticosterone response to repeated restraint stress and cold exposure and may be useful in studies of addiction and long-term neuroadaptations.

Detailed description

Urocortin is a corticotropin-releasing hormone family member and a stress-related neuropeptide involved in the hypothalamo-pituitary-adrenal axis and has been implicated in processes that link stress responses with addiction and long-term neuroadaptations. These mice carry a knockout allele of the Ucn (urocortin) gene. Homozygotes have elevated basal corticosterone levels. Male homozygotes do not adapt to repeated restraint stress, exhibiting increased corticosterone response when compared to wildtype controls. Female homozygotes display partial adaptation to repeated restraint stress. Homozygotes do not respond to 2 hours of cold exposure with elevated corticosterone levels. When cold exposure follows restraint stress, female homozygotes exhibit a significantly higher increase in circulating corticosterone levels when compared to wildtype controls, while male homozygotes exhibit no corticosterone response. Mice that are homozygous for the mutation are viable and fertile. No gene product (mRNA or protein) is detected by RT-PCR of total brain RNA or in situ hybridization analysis of Edinger-Westphal nucleus tissue from brain. During backcrossing, the Y chromosome may not have been fixed to the C57BL/6J genetic background.

Development

A targeting vector containing a NEO cassette was used to disrupt coding sequence after the initiation codon. The construct was electroporated into 129S4/SvJae derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The donating investigator reports that the resulting chimeric animals were crossed to C57BL/6 mice, and then backcrossed to C57BL/6 for 6 generations (see SNP note below). Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once 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. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, all 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a C57BL/6N genetic background.

Allele

Symbol: Ucn^tm1Abas
Name: targeted mutation 1, Abdul Abou-Samra
MGI accession ID: MGI:3716279
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Ucn
Marker name: urocortin
Chromosome: 5
Strain of origin: 129S4/SvJae
Molecular note: A targeting vector was designed to replace the coding sequence after the initiator methionine with a neomycin resistance cassette. In situ hybridization was used to confirm absence of protein expression.