B6;FVB-Tg(ACTA1-TRPC6*)1Jmol/J

Stock number: 024053
Product name: dnTRPC6 TG
Research areas: Cell Biology Research, Neurobiology Research

Description

Mice expressing this dominant negative form of human TRPC6 (dnTRPC6) rescue the muscular dystrophy phenotype of mice overexpressing TRPC3 cDNA under the control of a modified human ACTA1 promoter (Stock No. 024052).

Detailed description

TRPC (transient receptor potential canonical) channels have been implicated as mediators of unregulated calcium influx in dystrophic myofibers or myotubes.

This transgenic strain overexpresses a dominant-negative form of human TRPC6 (dnTRPC6) cDNA under the control of a modified human ACTA1 promoter. Western blot analysis has demonstrated protein overexpression in all skeletal muscles examined. The development or health of skeletal muscle is not negatively impacted, as assessed by histological methods.

When combined with a mutation that over-expresses TRPC3 in a model of muscular dystrophy (see Stock No. 024052), the dnTRPC6 transgene is found to significantly attenuate all aspects of disease associated with TRPC3 overexpression, including histophathology, the increase in small fiber numbers, and the number of myofibers with central nucleation.

Development

This transgene expresses a dominant negative form of human TRPC6 cDNA in which three highly conserved amino acids (L678-W680) within the putative pore region were replaced with alanine residues. The transgene is under the control of a modified human ACTA1 skeletal alpha-actin promoter (likely incorporating bp -2000 to +239). The transgenic vector was introduced to FVB embryos. Resultant founder lines were backcrossed minimally to C57BL/6. This line was maintained on a mixed C57BL/6-FVB genetic background by the donating laboratory.

Allele

Symbol: Tg(ACTA1-TRPC6*)1Jmol
Name: transgene insertion 1, Jeffery Molkentin
MGI accession ID: MGI:5516499
Generation method: Transgenic
Attributes: Dominant negative; Inserted expressed sequence; Humanized sequence
Marker symbol: Tg(ACTA1-TRPC6*)1Jmol
Marker name: transgene insertion 1, Jeffery Molkentin
Chromosome: UN
Strain of origin: FVB/N
Expressed genes: TRPC6,transient receptor potential cation channel subfamily C member 6,human
Molecular note: A modified human ACTA1 skeletal alpha-actin promoter (-2000 to +239drives muscle-specific expression of a dominant negative form of human TRPC6 cDNA in which three highly conserved amino acids (L678-W680) within the putative pore region were replaced with alanine residues. Line 1 was generated.