B6N.Cg-Htt^tm4Xen/80ChdiJ

Stock number: 027416
Product name: B6N.Hdh (CAGCAA)16 KI ; Hdh (CAGCAA)16 KI ; CHDI-81003013
Research areas: Neurobiology Research, Research Tools

Description

The Hdh (CAGCAA)16 knock-in allele has the human HTT exon 1 sequence with 80 glutamine repeats ([CAG CAA CAG CAA CAA]16) replacing the mouse Htt exon 1. These B6N.Hdh (CAGCAA)16 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.

Detailed description

Stock No. 027416 was formerly associated with CHDI Foundation colony Stock No. 370604 [CHDI-81003013].

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)16 knock-in (Hdh (CAGCAA)16 KI) allele replaces mouse Htt exon 1 with the human HTT exon 1 sequence with 80 glutamine repeats ([CAG CAA CAG CAA CAA]16]. 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.

Development

The Hdh (CAGCAA)16 knock-in (Hdh (CAGCAA)16 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 80 glutamine expansions ("mixed Htt (CAG CAA CAG CAA CAA)n; n = 16"). The targeting vector was microinjected into unspecified embryonic stem (ES) cells.

The Hdh (CAGCAA)16 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 (CAGCAA)16 KI), called CHDI Foundation colony Stock No. 370604 [CHDI-81003013]. In 2015, heterozygous animals with 80 glutamine repeats ([CAG CAA CAG CAA CAA]16) were sent from the CHDI Foundation colony to The Jackson Laboratory Repository, from which B6N.Hdh (CAGCAA)16 KI heterozygotes are available as Stock No. 027416.

Allele

Symbol: Htt^tm4Xen
Name: targeted mutation 4, Taconic Biosciences
MGI accession ID: MGI:5426951
Generation method: Targeted
Attributes: Humanized sequence
Marker symbol: Htt
Marker name: huntingtin
Chromosome: 5
Strain of origin: Not Specified
Molecular note: A construct carrying human exon 1 of Huntington gene with 80 CAG repeats (~80 glutamine expansions) was targeted to mouse Huntington gene replacing mouse exon 1 of the gene.