FVB/N-Tg(HSA*LR)20bCath/J

Stock number: 032031
Product name: HSA LR20b
Research areas: Neurobiology Research

Description

HSA LR20b transgenic mice express a human skeletal actin gene containing a CTG repeat expansion of approximately 220 repeats and exhibit some of the characteristics of myotonic dystrophy (DM). This strain may be useful for studying muscular dystrophy.

Detailed description

The HSA LR20b transgenic mice express a human skeletal actin gene (designated HSA) or ACTA1, containing a CTG repeat expansion of approximately 220 repeats. The transgene is expressed predominantly in skeletal muscle. Minor expression may occur in non-muscle cells, but has not been systematically examined. Myotonic dystrophy (DM) is the result of an expansion of a CTG repeat in the 3' untranslated region of the DMPK gene. HSA LR20b mice express an expanded CUG repeat in the human skeletal actin transgene mRNA, rather than the DMPK gene. HSA LR20b homozygous mice exhibit electromyographic myotonia as early as 4 weeks of age. Muscle histopathology is consistent with some of the characteristics of myotonic dystrophy (DM) including increases in central nuclei and ring fibers, and variability in fiber size in the absence of muscle fiber necrosis. However, these mice exhibit muscle weakness and degeneration that is less severe than myotonic dystrophy patients. This strain may be useful for studying muscular dystrophy.

The CTG repeat expansion size should be monitored in breeders at every generation.

The Jackson Laboratory breeds and distributes homozygous mice with CTG repeat expansion range of ~175-187 as determined by Laragen assay. Importantly, The Jackson Laboratory quality control group has used an alternate evaluation protocol to confirm the full expansion size of ~220 corresponds to Laragen assay size ~175-187. The Laragen assay quantification is consistently lower than the expected full expansion value as a result of their primer placement, design and evaluation protocol.

Development

The HSA LR20b transgene was designed by Dr. Charles A. Thornton (University of Rochester). The transgenic construct consists of the human skeletal actin gene (designated HSA) or ACTA1 modified to contain around 220 CTG repeat expansion inserted in the 3' untranslated region, midway between the termination codon and the polyA site. The construct was microinjected into FVB/N pronuclei. Founder line LR 20b (long repeat 20b) contains a single integration site with 2-3 copies of the transgene. The transgene is predominantly expressed only in skeletal muscle. The colony has been maintained on FVB/N.

The CTG repeat expansion size should be monitored in breeders at every generation.

The Jackson Laboratory breeds and distributes homozygous mice with CTG repeat expansion range of ~175-187 as determined by Laragen assay. Importantly, The Jackson Laboratory quality control group has used an alternate evaluation protocol to confirm the full expansion size of ~220 corresponds to Laragen assay size ~175-187. The Laragen assay quantification is consistently lower than the expected full expansion value as a result of their primer placement, design and evaluation protocol.

Allele

Symbol: Tg(HSA*LR)20bCath
Name: transgene insertion 20b, Charles A Thornton
MGI accession ID: MGI:3763907
Generation method: Transgenic
Attributes: Inserted expressed sequence; Humanized sequence
Marker symbol: Tg(HSA*LR)20bCath
Marker name: transgene insertion 20b, Charles A Thornton
Chromosome: UN
Strain of origin: FVB/N
Site of expression: The transgene is expressed predominantly in skeletal muscle.
Molecular note: The transgene contains human HSA with an expanded (250 repeats) CTG inserted into the last exon. Seven lines were created with expression restricted to skeletal muscle. This line contains 2 transgene insertions.