These huntingtin knock-in mice (originally termed HdhQ100) carry a mutant allele with a 100 CAG/polyQ repeat mutation, and may be useful in studies related to Huntington's disease.
Dr. Peter J Detloff, University of Alabama at Birmingham
Although the 100 CAG repeat length is similar to the repeat size range observed in a few patients with Huntington's disease, these mutant mice have no discernable abnormality upon casual inspection. Mice may have subtle defects not yet reported and might also serve as a control for repeat length dependent phenotype for longer repeat Hdh mutant strains. Mice homozygous for the targeted allele are viable and fertile. After 30 weeks of age mutant mice may become infertile.
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 100 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. The mice must be monitored for CAG/polyQ repeat length due to the instability of the repeat segment.
When using the B6.129P2-Htttm2Detl/100J mouse strain in a publication, please cite the originating article(s) and include JAX stock #016522 in your Materials and Methods section.