Cloning of the mouse dysferlin gene and genomic characterization of the SJL-Dysf mutation.
The SJL mouse strain has been widely used as an animal model for experimental autoimmune encephalitis (EAE), inflammatory muscle disease and lymphomas and has also been used as a background strain for the generation of animal models for a variety of diseases including motor neurone disease, multiple sclerosis and atherosclerosis. Recently the SJL mouse was shown to have myopathy due to dysferlin deficiency, so that it can now be considered a natural animal model for limb-girdle muscular dystrophy type 2B (LGMD2B) and Miyoshi myopathy (MM). We have cloned the mouse dysferlin cDNA and analysis of the sequence shows that the mouse dysferlin gene is characterized by six C2 domain sequences and a C-terminal anchoring domain, with the human and the mouse dysferlin genes sharing > 90% sequence homology overall. Genomic analysis of the SJL mutation confirms that the 171 bp RNA deletion has arisen by exon skipping resulting from a splice site mutation. The identification of this mutation has implications for the various groups using this widely available mouse stock.
Vafiadaki
E
E
School of Biochemistry and Genetics, University of Newcastle upon Tyne, UK.
Reis
A
A
Keers
S
S
Harrison
R
R
Anderson
L V
LV
Raffelsberger
T
T
Ivanova
S
S
Hoger
H
H
Bittner
R E
RE
Bushby
K
K
Bashir
R
R
D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D004195:Disease Models, Animal; D000073939:Dysferlin; D017353:Gene Deletion; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000235:genetics*; D009136:Muscular Dystrophies / Q000235:genetics; D009137:Muscular Dystrophy, Animal / Q000235:genetics*; D010641:Phenotype
C114839:DYSF protein, human; D000073939:Dysferlin; D008565:Membrane Proteins; D009124:Muscle Proteins