129S-Per2^tm1Drw/J

Stock number: 010832
Research areas: Neurobiology Research

Description

Mice that are homozygous for this targeted mutation of Per2, period homolog 2 (Drosophila), exhibit a short circadian period initially when housed in constant darkness, and then exhibit gradual loss of rhythmicity. Homozygotes exhibit phase shift responses to light. This mutant mouse strain may be useful in studies of circadian rhythm and sleep patterns.

Detailed description

Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Abberant gene products (mRNA) are detected by RT-PCR and RACE analysis of brain total RNA. No gene product (protein) is detected in homozygous mutant mice by immunohistochemical staining of superchiasmatic nuclei over a 24 hour period. Western blots of liver reveal a deletion mutant protein product is produced. When housed in constant darkness, homozygotes have a short circadian period initially, and then exhibit gradual loss of rhythmicity. Homozygotes exhibit phase shift responses to light. This mutant mouse strain may be useful in studies of circadian rhythm and sleep patterns.

Development

A targeting vector containing a PGKneo cassette was used to disrupt exon 5 and a portion of exon 6. The construct was electroporated into 129S4/SvJae derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. The resulting chimeric male animals were crossed to 129S4/SvJae female mice. Heterozygotes were intercrossed to generate homozygotes. Upon arrival at The Jackson Laboratory, mutant mice were bred with 129S1/SvImJ inbred mice (Stock No. 002448) for at least one generation to establish the colony.

Allele

Symbol: Per2^tm1Drw
Name: targeted mutation 1, David R Weaver
MGI accession ID: MGI:2182832
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Per2
Marker name: period circadian clock 2
Chromosome: 1
Strain of origin: 129S4/SvJae
Molecular note: Exon 5 and a portion of exon 6 were replaced with a neomycin selection cassette. Several transcript forms produced from the targeted allele were identified in homozygous mutant mice via RT-PCR and RACE analyses of brain RNA. The different transcripts involved aberrant splicing of exon 4 to a pseudoexon in intron 4, to a cryptic splice site within neo, and to exon 7. In spite of the transcripts having in-frame regions, normal protein was undetected in by immunohistochemical staining of superchiasmatic nuclei over a 24 hour period.