FVB-Tg(ACTA1*-TRPC3)1Jmol/J

Stock number: 024052
Research areas: Cell Biology Research, Neurobiology Research

Description

Mice overexpressing TRPC3 cDNA under the control of a modified human ACTA1 promoter show features of dystrophin-glycoprotein complex (DGC)-lacking dystrophic disease.

Detailed description

TRPC (transient receptor potential canonical) genes have been implicated in the development of muscular dystrophy.

These transgenic animals overexpress human transient receptor potential canonical 3 (TRPC3) cDNA driven by a modified human ACTA1 (actin, alpha 1, skeletal muscle) promoter. A 6-fold increase in expression can be seen in skeletal muscle, but not other organs or tissues. Immunohistochemistry from the quadriceps confirms that the overexpressed protein is appropriately localized to the sarcolemma. An increase in calcium influx results in a phenotype similar to dystrophin-glycoprotein complex (DGC)-lacking dystrophic disease. Transgenic animals show profound wasting of all skeletal muscles examined at 2 months of age, as determined by direct measurement of muscle weights. Histological analysis of the muscles reveals increased central nucleation of fibers (due to degeneration/regeneration cycles), increased numbers of small myofibers, fibrosis, and infiltration of inflammatory cells. Disease progresses and by 6 months of age, fatty tissue replacement can be seen throughout muscle, along with increased fibrosis and greater variations in fiber area distributions with prominent macrophage infiltration. The heart is unaffected.

Development

This transgene expresses full-length human TRPC3 cDNA 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 mice were maintained on an FVB genetic background by the donating laboratory.

Allele

Symbol: Tg(ACTA1-TRPC3)1Jmol
Name: transgene insertion 1, Jeffery Molkentin
MGI accession ID: MGI:5516498
Generation method: Transgenic
Attributes: Inserted expressed sequence; Humanized sequence
Marker symbol: Tg(ACTA1-TRPC3)1Jmol
Marker name: transgene insertion 1, Jeffery Molkentin
Chromosome: UN
Strain of origin: FVB
Expressed genes: TRPC3,transient receptor potential cation channel subfamily C member 3,human
Molecular note: A modified human ACTA1 skeletal alpha-actin promoter (-2000 to +239) was used to drive muscle-specific expression of full-length human TRPC3 cDNA. Line 1 was generated.