B6.Cg-Tg(ACTA1-cre)79Jme/J

Stock number: 006149
Product name: HSA-Cre79
Research areas: Neurobiology Research, Research Tools

Description

These transgenic mice have the cre recombinase gene driven by the human alpha-skeletal actin (HSA or ACTA1) promoter. When bred with mice containing a loxP-flanked sequence of interest, Cre-mediated recombination will result in striated muscle-specific deletion of the flanked genome. These mice are useful in study of spinal muscular atrophy (SMA).

Detailed description

Mice hemizygous for this HSA-Cre79 transgene are viable, fertile, normal in size, and do not display any gross physical or behavioral abnormalities. These HSA-Cre79 transgenic mice have the cre recombinase gene driven by the human alpha-skeletal actin (HSA or ACTA1) promoter. Cre activity is restricted to adult striated muscle fibers and embryonic striated muscle cells of the somites and heart. When bred with mice containing a loxP-flanked sequence of interest, Cre-mediated recombination will result in striated muscle-specific deletion of the flanked genome. Specifically, these HSA-Cre79 (or ACTA1-Cre) transgenic mice were originally used to breed with mice heterozygous for a deletion of exon 7 and a loxP-flanked exon 7 mutation on homologous chromosomes of the Smn1 gene (see Stock No. 006138 or Stock No. 006146). The resulting offspring (heterozygous for the deletion in all cells and homozygous for the deletion in striated muscle cells) have extremely reduced lifespan characterized by progressive muscle necrosis and paralysis, and represent a model of spinal muscular atrophy (SMA).

Additional SMA strains expressing cre in neurons are available as well (see Stock No. 005938, Stock No. 006297, and Stock No. 006663).

HSA-Cre79 transgenic mice are also available on a different genetic background (see Stock No. 006139). In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. It should be noted that the HSA-Cre79 phenotype could vary from that originally described on a mixed genetic background. We will modify the strain description if necessary as published results become available.

Importation of this model was supported by the Spinal Muscular Atrophy Foundation. Creation and development was supported by the National Institute of Health and Medical Research of France (Inserm) and the Association Française contre les Myopathies (AFM). An additional help was provided by Families of SMA (U.S.A.) and Andrew’s Buddies (U.S.A.).

Development

A targeting vector was designed to place a cre recombinase gene (preceded by the rabbit beta-globin intron and followed by the SV40 polyadenylation signal) under control of the human alpha-skeletal actin (HSA, ACTA1) promoter. This construct was microinjected into (C57BL6 x SJL)F1 embryos and implanted into pseudopregnant CD1 foster mothers. Founder 79 was bred to C57BL/6 to generate transgenic mice. At different points while maintaining this strain, transgenic mice were bred with C57BL/6 wild-type mice and/or mice harboring a loxP-flanked exon 7 mutation (Smn1^tm1Jme or SMN^F7) on a C57BL/6 and "129Sv" mixed background. Because expression of this transgene is confined to muscle tissue, Cre-mediated deletion of the floxed exon does not occur in the germline. Thus, offspring contained either the wild-type Smn1 locus or the floxed locus; never the Smn1 deletion. Transgenic offspring bearing the wild-type Smn1 locus on this mixed (but predominantly B6;129) background were sent to The Jackson Laboratory by Dr. Judith Melki in April 2006. After arriving, mutant mice were backcrossed to C57BL/6J (Stock No. 000664) for 5-10 generations.

Allele

Symbol: Tg(ACTA1-cre)79Jme
Name: transgene insertion 79, Judith Melki
MGI accession ID: MGI:2447635
Generation method: Transgenic
Attributes: Recombinase-expressing
Marker symbol: Tg(ACTA1-cre)79Jme
Marker name: transgene insertion 79, Judith Melki
Chromosome: UN
Strain of origin: (C57BL/6J x SJL)F1
Expressed genes: cre,cre recombinase,bacteriophage P1
Site of expression: adult striated muscle fibers and embryonic striated muscle cells of the somites and heart
Molecular note: This transgene expresses Cre recombinase under the control of a human alpha-skeletal actin promoter, active in striated muscle, heart, and skeletal muscle.