These HdhQ365 mice carry a mutant knock in allele with a 365 CAG/polyQ repeat mutation, and are expected to have a phenotype similar to the shorter length repeat versions derived 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
These HdhQ365 mice have yet to be fully characterized, but are expected to develop progressive neurological dysfunction by 1 year of age coincident with polyglutamine containing nuclear inclusions mostly in the striatal brain area. Heterozygote X heterozygote crosses fail to yield any homozygous progeny.
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 365 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. Heterozygote X heterozygote crosses fail to yield any homozygous progeny. The mice must be monitored for CAG/polyQ repeat length due to the instability of the repeat segment.
When using the B6.129P2-Htttm2Detl/365J mouse strain in a publication, please cite the originating article(s) and include JAX stock #021193 in your Materials and Methods section.