B6.129-Sgcd^tm1Mcn/J

Stock number: 004582
Product name: dsg-
Research areas: Cardiovascular Research, Mouse/Human Gene Homologs, Neurobiology Research

Description

These Sgcd knock-out mice exhibit early mortality with elevated creatine kinase serum levels and muscle degeneration.

Detailed description

Sarcoglycan, delta (dystrophin-associated glycoprotein)(Sgcd) is a multimeric, integral membrane glycoprotein complex that associates with dystrophin and has been associated with inherited forms of muscular dystrophy. Mice that are homozygous for the Sgcd knock-out allele (also known as dsg-) are viable, fertile, and normal in size at weaning age. However, at 8 weeks of age there is an onset of sudden mortality, with a 50% survival rate at 28 weeks. No gene product (protein) is immunodetected in skeletal muscle microsomal preparations.  Elevated creatine kinase serum levels are indicative of striated muscle degeneration. Histopathology of skeletal muscle tissue reveals degeneration and regeneration of muscle fibers, inflammatory infiltrate, perivascular fibrosis and calcification. At 12 weeks of age, cardiac muscle tissue also begins to show degeneration, inflammatory infiltration and perivascular fibrosis. Myofiber membranes have permeability defects as assessed by Evans blue dye uptake into myofiber cytoplasm. Skeletal muscle of mutant mice have an enhanced sensitivity to mechanically induced sarcolemmal damage. This mutant mouse strain may be useful in studies of limb girdle muscular dystrophy and cardiomyopathy.

Development

A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt exon 2, which encodes the initiation site, cytoplasmic domain and transmembrane domain. The construct was electroporated into 129 derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric male animals were crossed to 129T2/SvEmsJ (Stock No. 002065) mice and then backcrossed to C57BL/6 for more than 10 generations before males were sent to The Jackson Laboratory in 2003. Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes (Stock No. 000664).

Allele

Symbol: Sgcd^tm1Mcn
Name: targeted mutation 1, Elizabeth M McNally
MGI accession ID: MGI:2180193
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Sgcd
Marker name: sarcoglycan, delta (dystrophin-associated glycoprotein)
Chromosome: 11
Strain of origin: (129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Molecular note: A neomycin selection cassette was used to replace exon 2, which encodes the translation initiation codon and the cytoplasmic and transmembrane domains. Northern analysis showed that message was not transcribed in skeletal muscle of homozygous mutant mice. The lack of protein in immunoblots further confirmed complete inactivation.