129S-Per3^tm1Drw/J

Stock number: 010833
Research areas: Neurobiology Research

Description

Male mice that are homozygous for this targeted mutation of Per3, period homolog 2 (Drosophila), exhibit a shorter free running period when housed in constant darkness. 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. No gene product (protein) is detected by Western blot analysis of whole brain minus cerebellum and hypothalamus, whole hypothalamus, and anterior hypothalamus containing SCN, from homozygotes. Immunoprecipitation analysis of brain lysates from homozygotes does not detect any gene product (protein). Abberant gene products (mRNA) are detected by Northern blot analysis and RT-PCR, and have rhythmic expression. Under conditions of constant darkness, homozygous males exhibit a shorter free running period. A subset of mice exhibit progressive shortening of the period length in extended constant darkness. This mutant mouse strain may be useful in studies of circadian rhythm and sleep patterns.

Please note: Mice derived from 129S-Per3^tm1Drw/J are reported to a carry a spontaneous deletion in exon 3 of the Mfrp gene (174delG or rdx) that causes photoreceptor degeneration and eventual retinal pigment epithelium. It is unknown if the Per3 KO carries the mutation. (IOVS 2011 52(10):7256)

Development

A targeting vector containing a PGKneo cassette was used to disrupt exon 3 and part of exon 4. 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 female 129S4/SvJae 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: Per3^tm1Drw
Name: targeted mutation 1, David R Weaver
MGI accession ID: MGI:2385797
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Per3
Marker name: period circadian clock 3
Chromosome: 4
Strain of origin: 129S4/SvJae
Molecular note: The gene was disrupted by replacement of exon 3 and part of exon 4 (encoding amino acids 92-154) with a PGK-neo cassette via homologous recombination. Introduction of PGK-neo introduces stop codons into all 3 reading frames. Western blot analysis of brain lysates from homozygous mutant animals using antibodies directed against the C-terminus of the protein confirmed the absence of protein expression. Immunoprecipitation assays also confirmed the absence of protein product. Northern blot and RT-PCR analysis detected mutant transcripts containing neo and lacking exon 3 and part of exon 4 in brain and skeletal muscles from homozygous mutants.