B6.Cg-Gt(ROSA)26Sor^{tm38(H1/tetO-RNAi:Htt)Arte}/ChdiJ

Stock number: 027436
Product name: B6.Hdh RNAiTT ; Hdh (CHD-032) ; CHDI-81002002
Research areas: Neurobiology Research, Research Tools

Description

The Hdh RNAiTT targeted mutation allows tetracycline-inducible, huntingtin-specific short hair pin RNA (shRNA) expression, and is driven by the H1 RNA polymerase III promoter within the endogenous mouse Gt(ROSA)26Sor locus. These mice allow Tet-inducible/controllable Htt knock-down, and are useful for studying Huntington's disease.

Detailed description

Stock No. 027436 was formerly associated with CHDI Foundation colony Stock No. 370535 [CHDI-81002002].

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 RNAiTT targeted mutation allows tetracycline-inducible, huntingtin-specific short hair pin RNA (shRNA) expression, and is driven by the H1 RNA polymerase III promoter within the endogenous mouse Gt(ROSA)26Sor locus. These mice allow Tet-inducible/controllable Htt knock-down. Heterozygous mice are expected to be viable and fertile. The phenotype of these mice is not further characterized to date (August 2015).

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

Development

The Hdh RNAiTT targeted mutation was designed by Taconic Artemis to have the H1 RNA polymerase III promoter coupled to a tet-operator (tetO) sequence (H1-tetO) and a huntingtin-specific short hair pin RNA (shRNA) sequence all inserted into the mouse Gt(ROSA)26Sor locus on chromosome 6 using RCME. Mice were sent to the CHDI Foundation colony as colony Stock No. 370535 [CHDI-81002002]. The colony was reported to be on the C57BL/6J genetic background (but SNP results in 2016 indicate C57BL/6N; see below). In 2015, sperm frozen from the CHDI Foundation colony was thawed and used to fertilize C57BL/6J oocytes (Stock No. 000664); the resulting live mice were sent to The Jackson Laboratory Repository - from which B6.Hdh RNAiTT heterozygotes are available as Stock No. 027436.

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, 5 of 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating in all mice tested (chromosomes 8 [~15.2 Mbp], 11 [~4.4 Mbp], 13 [~41.0 Mbp], 15 [~57.6 Mbp] and 19 [~49.9 Mbp]). These data suggest that the sperm used to create The Jackson Laboratory Repository colony was on a C57BL/6N genetic background.

Allele

Symbol: Gt(ROSA)26Sor^{tm38(H1/tetO-RNAi:Htt)Arte}
Name: targeted mutation 38, TaconicArtemis
MGI accession ID: MGI:5426914
Generation method: Targeted
Attributes: Inducible; RMCE-ready; Knockdown
Marker symbol: Gt(ROSA)26Sor
Marker name: gene trap ROSA 26, Philippe Soriano
Chromosome: 6
Strain of origin: Not Specified
Molecular note: A short hairpin RNA (shRNA) against the Huntington gene was placed under the control of the H1-tetO promoter and targeted to Gt(ROSA)26Sor locus by RMCE.