The Hdh (CAGCAA)21 knock-in allele has the human HTT exon 1 sequence with ~105 glutamine repeats ([CAG CAA CAG CAA CAA]21) replacing the mouse Htt exon 1. These B6N.Hdh (CAGCAA)21 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. 027418 was formerly associated with CHDI Foundation colony Stock No. 370608 [CHDI-81003015].
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 (CAGCAA)21 knock-in (Hdh (CAGCAA)21 KI) allele replaces mouse Htt exon 1 with the human HTT exon 1 sequence with ~105 glutamine repeats ([CAG CAA CAG CAA CAA]21]. 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.
The Hdh (CAGCAA)21 knock-in (Hdh (CAGCAA)21 KI) allele 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 105 glutamine expansions ("mixed Htt (CAG CAA CAG CAA CAA)n; n = 21"). The targeting vector was microinjected into unspecified embryonic stem (ES) cells.
The Hdh (CAGCAA)21 KI mice were sent to the CHDI Foundation, and then backcrossed several generations with C57BL/6NJ inbred mice (Stock No. 005304) to create the C57BL/6N-congenic colony (B6N.Hdh (CAGCAA)21 KI), called CHDI Foundation colony Stock No. 370604 [CHDI-81003013]. In 2015, heterozygous animals with 101 glutamine repeats ([CAG CAA CAG CAA CAA]21) from backcross generation N6-N7 were sent from the CHDI Foundation colony to The Jackson Laboratory Repository, from which B6N.Hdh (CAGCAA)21 KI heterozygotes are available as Stock No. 027418.
|Allele Name||targeted mutation 6, Taconic Biosciences|
|Allele Type||Targeted (Inserted expressed sequence, 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 21 CAG CAA CAG CAA CAA repeats (~105 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 (CAGCAA)21 KI ; Hdh (CAGCAA)21 KI ; CHDI-81003015 mouse strain in a publication, please cite the originating article(s) and include JAX stock #027418 in your Materials and Methods section.