The Hdh CAG 80 knock-in allele (Hdh CAG80 KI) has the human HTT exon 1 sequence with an ~80 polyglutamine expansion comprised of a pure CAG expansion [(CAG)78CAACAG] replacing the mouse Htt exon 1. These B6N.Hdh CAG80 KI mice may be useful for studying Huntington's disease, specifically the effect of interrupted CAG tracts versus pure CAG tracts on somatic instability and RNA structure mechanisms in HD pathophysiology.
Dr. David Howland, CHDI Foundation
David S Grass, Taconic Biosciences (formerly Xenogen Biosciences)
Stock No. 027415 was formerly associated with CHDI Foundation colony Stock No. 370610 [CHDI-81003012].
Huntington's disease (HD) is an autosomally dominant, fatal neurodegenerative disorder characterized by uncontrolled movements, psychiatric disturbances and cognitive impairment. HD is caused by an unstable trinucleotide (polyglutamine) repeat expansion in the huntingtin gene (HTT; HD or Hdh).
The Hdh CAG 80 knock-in allele (Hdh CAG80 KI) replaces mouse Htt exon 1 with the human HTT exon 1 sequence containing an 80 polyglutamine expansion comprised of a pure CAG expansion [(CAG)78CAACAG]. The CAG repeat number is subject to germline and somatic instability, and may expand or contract (see note on CAG instability below). Heterozygous mice are viable and fertile. These mice have not been further characterized to date (April 2014), but may be useful in applications exploring the effect of interrupted CAG tracts versus non-interrupted CAG tracts on somatic instability and RNA structure mechanisms in HD pathophysiology.
This Huntington's disease mouse model is available by way of a collaborative effort between CHDI Foundation, Dr. David S. Grass (Xenogen Biosciences [now Taconic Biosciences]), and The Jackson Laboratory.
Expanded CAG sequences in huntingtin exon 1 may be subject to germline or somatic instability, and may expand or contract. When using lines with unstable CAG repeat length, it is strongly recommended the CAG repeat number be quantified in all the experimental animals; all animals in all experimental groups should carry comparable CAG repeat sizes. CAG repeat sizing of HD mice should be done using high-resolution methods as assays based on agarose gel electrophoresis typically do not provide sufficient resolution to accurately measure CAG repeat numbers. If labs do not have access to the appropriate equipment for determining CAG repeat length, CAG repeats can be evaluated on a fee-for-service basis by Laragen, Inc.
The Hdh CAG 80 knock-in allele (Hdh CAG80 KI) was designed by Dr. David S. Grass (while at Xenogen Biosciences [now Taconic Biosciences]). A targeting vector was designed to replace mouse huntingtin (Htt; HD or Hdh) exon 1 with a human HTT exon 1 sequence containing an 80 polyglutamine expansion comprised of a pure CAG expansion [(CAG)78CAACAG]. The targeting vector was microinjected into unspecified embryonic stem (ES) cells.
The Hdh CAG80 KI mice were backcrossed with C57BL/6N inbred mice for 5-10 generations, sent to the CHDI Foundation, and then backcrossed an additional four generations with C57BL/6NJ inbred mice (Stock No. 005304) to create the C57BL/6N-congenic colony (B6N.Hdh CAG80 KI), called CHDI Foundation colony Stock No. 370610 [CHDI-81003012]. In 2015, heterozygous animals with ~78 CAG repeats were sent from the CHDI Foundation colony to The Jackson Laboratory Repository, from which B6N.Hdh CAG80 KI heterozygotes are available as Stock No. 027415.
|Allele Name||targeted mutation 3, Taconic Biosciences|
|Allele Type||Targeted (Humanized sequence)|
|Gene Symbol and Name||Htt, huntingtin|
|Strain of Origin||Not Specified|
|Molecular Note||A construct carrying human exon 1 of Huntington gene with 16 CAG CAA CAG CAA CAA repeats (~80 glutamine expansions) was targeted to mouse Huntington gene replacing mouse exon 1 of the gene.|
When maintaining our live colony, heterozygous mice are bred to C57BL/6NJ inbred mice (Stock No. 005304).
When using the B6N.Hdh CAG80 KI ; Hdh CAG 80 KI ; CHDI-81003012 mouse strain in a publication, please cite the originating article(s) and include JAX stock #027415 in your Materials and Methods section.