STOCK Tg(ACTA1-Thbs4)2Jmol/J

Stock number: 036161
Product name: Ska-Thbs4-Tg, Thbs4-Tg
Research areas: Neurobiology Research

Description

Thbs4-Tg mice express full-length mouse Thbs4 (thrombospondin 4) cDNA from the human ACTA1 (actin, alpha 1, skeletal muscle) promoter in skeletal muscle. This strain is useful in studies of muscle degenerative diseases such as muscular dystrophy (MD).

Detailed description

THBS4 (thrombospondin 4), a critical cardioprotective protein functioning from within the endoplasmic reticulum (ER), binds directly with the ER luminal domain of ATF6 (activating transcription factor 6) to promote its shuttling to the Golgi and then nucleus, thereby inducing genes underlying adaptive aspects of ER stress responses.

Thbs4-Tg mice express full-length mouse Thbs4 cDNA from the human ACTA1 (actin, alpha 1, skeletal muscle) promoter in skeletal muscle. While these mice do not display an overt baseline phenotype, skeletal muscle-specific overexpression of mouse Thbs4 is protective and mitigates dystrophic disease. More specifically, besides inducing an adaptive ATF6 (ATF6α)-mediated unfolded protein response, Thbs4 selectively enhances vesicular trafficking of dystrophin-glycoprotein and integrin attachment complexes to stabilize the sarcolemma of the myofiber and thereby protects the muscle from dystrophic disease.

Development

A transgenic vector incorporating a modified human ACTA1 (also called skeletal α-actin, Ska, or human skeletal actin (HSA)) promoter driving expression of full-length mouse Thbs4 cDNA was introduced to FVB/N embryos. The modified promoter incorporates 2 kb of 5' flanking sequence, 90 bases of 5'-UTR, and 149 bases of IVS1 (intervening sequence 1) from the human ACTA1 gene. Resultant mice were maintained on the FVB/N genetic background by the donating laboratory (see SNP note below). This is founder line 2. The integration site and copy number of the transgene are not known (February, 2021).

In 2021, a 48 SNP (single nucleotide polymorphism) panel analysis, with 43 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 males sent to The Jackson Laboratory Repository. Three of the 43 markers throughout the genome were segregating with an unknown source, on Chromosome 1, 9, and the X Chromosome.

Allele

Symbol: Tg(ACTA1-Thbs4)2Jmol
Name: transgene insertion 2, Jeffery Molkentin
MGI accession ID: MGI:6505475
Generation method: Transgenic
Attributes: Inserted expressed sequence
Synonyms: Thbs4 Tg
Marker symbol: Tg(ACTA1-Thbs4)2Jmol
Marker name: transgene insertion 2, Jeffery Molkentin
Chromosome: UN
Strain of origin: FVB/N
Molecular note: The transgenic vector contains a modified human ACTA1promoter driving expression of full-length mouse Thbs4 cDNA. The modified promoter incorporates 2 kb of 5' flanking sequence, 90 bases of 5'-UTR, and 149 bases of IVS1 (intervening sequence 1) from the human ACTA1 gene.