B6.A-Dysf^prmd/GeneJ

Stock number: 012767
Product name: BLAJ
Research areas: Mouse/Human Gene Homologs, Neurobiology Research

Description

These Bl/AJ (BlAJ or Bla/J) mice have the progressive muscular dystrophy allele of dysferlin (Dysf^prmd) from the A/J inbred strain introgressed into the C57BL/6 genetic background. Bl/AJ mice display centronucleated fibers and progressive muscle weakness, and may be useful as a model of limb-girdle muscular dystrophy type 2B (LGMD2B) and Miyoshi myopathy.

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Detailed description

In these Bl/AJ (BlAJ or Bla/J) mice, the progressive muscular dystrophy allele (prmd) from the A/J inbred strain is introgressed into the C57BL/6 genetic background. Disease onset is observed by 2 months and is characterized by the presence of centronucleated fibers and areas of inflammation. As seen with the original background A/J, mice homozygous for the prmd allele on the C57BL/6J background display an increasing number of centronucleated fibers and impairment in the majority of muscles by 4 months of age. In order of severity, the most affected muscles are psoas, quadriceps femoris, tibialis anterior, and gastrocnemius. Mice exhibit a decreased membrane repair capacity following laser wounding experiments. In an open space assay, mice cover less distance and are less active than wild-type. Mice that are homozygous for this allele are viable, fertile and normal in size. This mutant mouse strain may be useful as a model of limb-girdle muscular dystrophy type 2B (LGMD2B) and Miyoshi myopathy.

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 phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

This strain was made available with the assistance of the Jain Foundation.

Development

The progressive muscular dystrophy (prmd) allele was first identified as a strain characteristic of the A/J inbred strain at The Jackson Laboratory in 2004. The mutation was determined to be a retrotransposon insertion in intron 4 resulting in aberrant splicing and absence of the dysferlin protein. The prmd allele was introgressed into C57BL/6 in the laboratory of Dr. Isabelle Richard (Genethon), and the B6-congenic line was called Bl/AJ (BlAJ or Bla/J). The Bl/AJ strain was transferred to Dr. Douglas E. Albrecht of the Jain Foundation where the backcross generation reached N8. In collaboration with the Jain Foundation, Dr. Richard donated the Bl/AJ strain to The Jackson Laboratory Repository in 2010. Upon arrival, mice were bred to C57BL/6J for at least 2 generations to establish the colony.

Allele

Symbol: Dysf^prmd
Name: progressive muscular dystrophy
MGI accession ID: MGI:3055150
Generation method: Spontaneous
Attributes: Null/Knockout
Marker symbol: Dysf
Marker name: dysferlin
Marker synonyms: 2310004N10Rik; FER1L1; LGMD2B; LGMDR2; MMD1
Chromosome: 6
Strain of origin: A/J
Molecular note: A retrotransposon insertion occurred within intron 4, causing aberrant splicing of the gene. Protein was abolished as shown by Northern blot and immunoblot analysis. The insertion was 6000bp in size. This allele was found only in A/J mice, not in A/WySnJ, A/HeJ, C57BL/6J, SJL/J, SWR/J or 129/SvJ mice.