These huntingtin knock-in mice (originally termed HdhQ315) carry a mutant allele with a 315 CAG/polyQ repeat mutation, and exhibit an earlier onset of phenotype as compared to the HdhQ150 strain (STOCK no. 4595). This mutant strain may be useful in studies related to Huntington's disease.
Dr. Peter J Detloff, University of Alabama at Birmingham
HdhQ315 mutant mice exhibit a visibly abnormal phenotype at an earlier age when compared to the HdhQ150 strain (STOCK no. 004595 ), but have yet to be fully characterized. Mutant CAG/polyQ repeat expression is slightly lower than wildtype levels as detected by Western blot analysis and qRTPCR of brain tissue. Mutant mice may be noticeably smaller than wild-type littermates. Mice homozygous for the targeted allele are viable and fertile. Onset of symptoms occurs earlier for homozygotes than for heterozygotes. After 20 weeks of age mutant mice may become infertile. The Donating Investigator reports that homozygotes do not breed well.
In the first step of a two step procedure, exon 1 was replaced with the selectable marker Hprt in 129P2/OlaHsd-derived HM1 embryonic stem (ES) cells. A second round of targeting was performed to replace Hprt with exon 1 sequence including a 150 CAG repeat segment. Correctly targeted ES cells were injected into C57BL/6J blastocysts. Before being donated to the Repository, the mice were backcrossed to C57BL/6J for 12 generations while being selectively bred for the 315 CAG repeat segment which arose due to repeat instability. Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the colony. The mice must be monitored for CAG repeat length due to the instability of the repeat segment.
|Allele Name||targeted mutation 2, Peter J Detloff|
|Allele Synonym(s)||CHL2; Hdh(CAG)150; HdhQ150; Hdh150Q; Hdh200Q; HdhCAG150; HdhQ150; HdhQ200|
|Gene Symbol and Name||Htt, huntingtin|
|Promoter||Htt, huntingtin, mouse, laboratory|
|Strain of Origin||129P2/OlaHsd-Hprtb-m3|
|Molecular Note||This allele carries 150 CAG repeat units in the first exon of the endogenous gene. CAG repeat numbers in this gene are highly unstable. Mice carrying this allele may have more or fewer repeats than stated in the original description.|
When maintaining a live colony, breeding C57BL/6J females with heterozygous males is suggested to help stabilize the CAG/polyQ repeat segment length. After 20 weeks of age mutant mice may become infertile. The Donating Investigator reports that homozygotes do not breed well. The mice must be monitored for CAG/polyQ repeat length due to the instability of the repeat segment.
When using the B6.129P2-Htttm2Detl/315J mouse strain in a publication, please cite the originating article(s) and include JAX stock #016525 in your Materials and Methods section.