B6.Cg-Htt^tm1(HTT)Arte/ChdiJ

Stock number: 027435
Product name: B6.Hd(HD_1000aa) KI ; HQ0022-HD 1000(aa)TT ; CHDI-81003009
Research areas: Neurobiology Research, Research Tools

Description

The Hd(HD_1000aa) KI targeted mutation has a CAG promoter and human huntingtin fragment encoding the first 1000 amino acids (with 145 mixed CAA-CAG repeats) replacing a partial promoter region and exon 1 of the endogenous Htt locus. These mice may be useful for studying Huntington's disease.

Detailed description

Stock No. 027435 was formerly associated with CHDI Foundation colony Stock No. 370266 [CHDI-81003009].

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 Hd(HD_1000aa) KI targeted mutation has a CAG promoter and human huntingtin fragment encoding the first 1000 amino acids (with 145 mixed CAA-CAG repeats [see polyQ assay note below]) replacing a partial promoter region and exon 1 of the endogenous Htt locus. Endogenous Htt gene expression is disrupted. Heterozygous mice are expected to be viable and fertile. The phenotype of these mice is not further characterized to date (August 2015).
Important note on polyQ assay: the polyQ repeat assay shows heterozygous mice maintain a stable 141 polyQ repeat length.

This Huntington's disease mouse model is available by way of a collaborative effort between CHDI Foundation, Taconic Artemis and The Jackson Laboratory.

Development

A targeting vector was designed to replace a partial promoter region and exon 1 of the mouse huntingtin locus (Htt; HD or Hdh) with a CAGGS promoter sequence and cDNA encoding a mutant human HTT gene (145Q [see polyQ assay note below]) truncated at position ~aa1000 (Difiglia site). Mice were sent to the CHDI Foundation colony as Stock No. 370266 [CHDI-81003009]. The colony is reported to be on the C57BL/6J genetic background. In 2015, animals were sent from the CHDI Foundation colony to The Jackson Laboratory Repository, from which B6.Hd(HD_1000aa) KI heterozygotes are available as Stock No. 027435.
Important note on polyQ assay: the polyQ repeat assay shows heterozygous mice maintain a stable 141 polyQ repeat length.

In 2016, a 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the first generation rederived living colony at The Jackson Laboratory Repository. While the 27 markers throughout the genome were all found to be C57BL/6 allele-type, 4 of the 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating in the cohort of mice tested (chromosomes 8 [~15.2 Mbp], 13 [~41.0 Mbp], 15 [~57.6 Mbp] and 19 [~49.9 Mbp]); individual mice had 2-3 markers segregating. These data suggest that the mice sent to The Jackson Laboratory Repository colony were on a mixed C57BL/6J;C57BL/6N genetic background.

Allele

Symbol: Htt^tm1(HTT)Arte
Name: targeted mutation 1, TaconicArtemis
MGI accession ID: MGI:5426926
Generation method: Targeted
Attributes: Null/Knockout; Inserted expressed sequence
Marker symbol: Htt
Marker name: huntingtin
Chromosome: 5
Strain of origin: Not Specified
Molecular note: A cDNA construct carrying mutant human Huntington gene (145Q) truncated at position ~aa1000 (Difiglia site) under the control of CAGGS promoter was targeted into endogenous mouse Htt locus. Endogenous Htt gene expression was disrupted due to deletion of partial promoter region and exon 1.