B6.129S7-Cacna1a^tm1Hzo/J

Stock number: 008816
Research areas: Neurobiology Research

Description

These knock-in mice carry a hyperexpanded (14-copy) polyglutamine (CAG) repeat in the targeted Cacna1a (calcium channel, voltage-dependent, P/Q type, alpha 1A subunit) gene. Homozygous Sca6^14Q/14Q and heterozygous Sca6^14Q/+ mice are indistinguishable from wild-type littermates, even after 20 months of age.

Detailed description

These knock-in mice carry a hyperexpanded (14-copy) polyglutamine (CAG) repeat in the targeted Cacna1a (calcium channel, voltage-dependent, P/Q type, alpha 1A subunit) gene. Homozygous Sca6^14Q/14Q and heterozygous Sca6^14Q/+ mice are indistinguishable from wild-type littermates, even after 20 months of age.

Development

A segment of mouse exon 47 was replaced by the homologous human genomic segment containing 14 copies of a CAG repeat. A neomycin resistance cassette and thymidine kinase gene flanked by a pair of loxP sites were inserted into exon 45 of the mouse gene. The targeting vector was introduced to AB2.2 129S7/SvEvBrd-Hprt1⁺-derived embryonic stem (ES) cells and subsequent electroporation of Cre-recombinase plasmids into positive clones excised the floxed segment. This line was backcrossed 12 times to C57BL/6 by the donating laboratory.

Allele

Symbol: Cacna1a^tm1Hzo
Name: targeted mutation 1, Huda Y Zoghbi
MGI accession ID: MGI:3810386
Generation method: Targeted
Attributes: Humanized sequence
Synonyms: Cacna1a^hEx47; Sca6^14Q
Marker symbol: Cacna1a
Marker name: calcium channel, voltage-dependent, P/Q type, alpha 1A subunit
Marker synonyms: alpha1A; APCA; BccA1; BI; CACNL1A4; Cav2.1; Ccha1a; DEE42; EA2; EIEE42; FHM; HPCA; MHP; MHP1; nmf352; rbA-1; SCA6; smrl
Chromosome: 8
Strain of origin: 129S7/SvEvBrd-Hprt1^b-m2
Molecular note: A floxed neo cassette was inserted upstream of exon 46 and exon 47 was replaced with its human equivalent. During the process the number of CAG repeats was modified to 14, and transient cre expression was used to remove the floxed neo cassette.