Male mice that are homozygous for this targeted mutation of Per3, period homolog 3 (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.
David R. Weaver, Univ of Massachusetts Medical School
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.
In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. This is the case for the strain above. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.
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 129/sv mice, and then backcrossed to C57BL/6J for 10 generations.
|Allele Name||targeted mutation 1, David R Weaver|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Per3, period circadian clock 3|
|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.|
|Mutations Made By|| |
Shin Yamazaki, Vanderbilt University
When maintaining a live colony, these mice can be bred as homozygotes.
When using the B6.129S4-Per3tm1Drw/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #010493 in your Materials and Methods section.