B6.Cg-Gt(ROSA)26Sor^{tm49(HTT)Arte}/ChdiJ

Stock number: 027428
Product name: B6.HD_DS536(TT);HQ-019 ; HQ0019 (HD_S536(TT)) ; CHDI-81002019
Research areas: Neurobiology Research, Research Tools

Description

The HD_DS536(TT);HQ-019 targeted mutation has the S536 HTT transgene (human huntingtin fragment encoding the first 536 amino acids with 145 mixed CAA-CAG repeats) inserted into the mouse Gt(ROSA)26Sor locus. The polyQ repeat assay shows heterozygous mice over several generations have a stable 141 polyQ repeat. These mice are part of a series expressing different human HTT amino acid length fragments, and may be useful for studying comparable patterns and levels of HTT expression in Huntington's disease.

Detailed description

Stock No. 027428 was formerly associated with CHDI Foundation colony Stock No. 370346 [CHDI-81002019].

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_DS536(TT);HQ-019 targeted mutation has the CMV early enhancer/chicken beta actin promoter driving expression of the S536 HTT transgene (human HTT fragment encoding the first 536 amino acids with 145 mixed CAA-CAG repeats [see polyQ assay note below]) from the mouse Gt(ROSA)26Sor locus. 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: over several generations, the polyQ repeat assay shows heterozygous mice have maintained 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.

These mice are part of a series expressing different human HTT amino acid length fragments from Gt(ROSA)26Sor. All are reported to have a stable array of 145 mixed CAA-CAG repeats (see polyQ assay note above) and are on the C57BL/6 genetic background. Together, they are useful in studying comparable patterns and levels of HTT expression. The series includes:
HD_N171(TT);HQ-021 mice are Stock No. 027426
HD_A463(TT);HQ-020 mice are Stock No. 027427
HD_DS536(TT);HQ-019 mice are Stock No. 027428
HD_D552(TT);HQ-017 mice are Stock No. 027429
HD_D586(TT);HQ-016 mice are Stock No. 027430
HD_1000aa(TT);HQ-022 mice are Stock No. 027431

Development

The HD_DS536(TT);HQ-019 targeted mutation was designed by Taconic Artemis to have the CMV early enhancer/chicken beta actin promoter sequence and the S536 HTT transgene all inserted into the mouse Gt(ROSA)26Sor locus on chromosome 6. The S536 HTT sequence has a human huntingtin [HTT] fragment encoding the first 536 amino acids (with 145 mixed CAA-CAG repeats [see polyQ assay note below]). Mice were sent to the CHDI Foundation colony as Stock No. 370346 [CHDI-81002019]. The colony is reported to be on the C57BL/6 genetic background. In 2015, animals were sent from the CHDI Foundation colony to The Jackson Laboratory Repository, from which B6.HD_DS536(TT);HQ-019 heterozygotes are available as Stock No. 027428.
Important note on polyQ assay: over several generations, the polyQ repeat assay shows heterozygous mice have maintained 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, all 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], 11 [~4.4 Mbp], 13 [~41.0 Mbp], 15 [~57.6 Mbp] and 19 [~49.9 Mbp]); individual mice had 3 or 4 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.

Furthermore, a cohort of first generation heterozygous mice in our rederived living colony all tested as having a neomycin resistance cassette - suggesting the HD_DS536(TT);HQ-019 targeted mutation also includes a neo cassette.

Allele

Symbol: Gt(ROSA)26Sor^{tm49(HTT)Arte}
Name: targeted mutation 49, TaconicArtemis
MGI accession ID: MGI:5426929
Generation method: Targeted
Attributes: Inserted expressed sequence; RMCE-ready
Synonyms: N536-Q148
Marker symbol: Gt(ROSA)26Sor
Marker name: gene trap ROSA 26, Philippe Soriano
Marker synonyms: beta geo; Gtrgeo26; Gtrosa26; R26; ROSA26; SETD5-AS1; Thumpd3as1
Chromosome: 6
Strain of origin: Not Specified
Molecular note: A cDNA construct carrying mutant human Huntington gene (145Q) truncated at position aa S536 under the control of the CMV early enhancer/chicken beta actin promoter was targeted into Gt(ROSA)26Sor locus by RMCE.