Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Congenic; Mutant Strain; Spontaneous Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse Generation N9+N1pN1 Generation Definitions   Donating Investigator Dr. Isabelle Richard,   Genethon

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.

Control Information

	Control
	Wild-type from the colony
	000664 C57BL/6J
Considerations for Choosing Controls

Related Strains

Strains carrying   Dysf^prmd allele

000646	A/J
017917	B6.Cg-Dysfprmd Prkdcscid/J

View Strains carrying   Dysf^prmd     (2 strains)

Strains carrying other alleles of Dysf

006830	129-Dysftm1Kcam/J
011128	B10.SJL-Dysfim/AwaJ
013149	B6.129-Dysftm1Kcam/J
017644	B6;129S6-Dysftm2.1Kcam/J
000686	SJL/J

View Strains carrying other alleles of Dysf     (5 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

- Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

Miyoshi Muscular Dystrophy 1; MMD1
Muscular Dystrophy, Limb-Girdle, Type 2B; LGMD2B
Myopathy, Distal, with Anterior Tibial Onset; DMAT

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Dysf^prmd/Dysf^prmd

        A/J

• behavior/neurological phenotype
• abnormal physical strength   (MGI Ref ID J:92838)
• limb grasping
  • hind-limb clasping develops after 8 months of age   (MGI Ref ID J:92838)
  • inability to spread legs when suspended by their tails after 8 months of age   (MGI Ref ID J:92838)
• muscle phenotype
• abnormal skeletal muscle morphology
  • perivascular infiltrates and inflammation seen by 8 months of age   (MGI Ref ID J:92838)
  • eventually, active myopathy was seen in all skeletal muscles   (MGI Ref ID J:92838)
• • abnormal skeletal muscle fiber morphology
    • abnormalities primarily in proximal muscles at early ages   (MGI Ref ID J:92838)
    • hypertrophic fibers, fiber splitting and fat replacement also seen   (MGI Ref ID J:92838)
  • • centrally nucleated skeletal muscle fibers   (MGI Ref ID J:92838)
    • skeletal muscle fiber degeneration
      • fibers with scattered degenerating and regenerating fibers by 4-5 months of age   (MGI Ref ID J:92838)
    • skeletal muscle fiber necrosis
      • increased numbers of necrotic and regenerating fibers with time   (MGI Ref ID J:92838)
  • skeletal muscle endomysial fibrosis
    • endomysial fibrosis at later stages   (MGI Ref ID J:92838)

View Research Applications

Research Applications

This mouse can be used to support research in many areas including:

Mouse/Human Gene Homologs
muscular dystrophy, limb-girdle
      type 2B

Neurobiology Research
Muscular Dystrophy
      Limb-Girdle type

Dysf^prmd related

Mouse/Human Gene Homologs
muscular dystrophy, limb-girdle
      type 2B

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Dysfprmd
Allele Name		progressive muscular dystrophy
Allele Type		Spontaneous
Mutation Made By		Douglas Albrecht,   Jain Foundation Inc
Strain of Origin		A/J
Gene Symbol and Name		Dysf, dysferlin
Chromosome		6
Gene Common Name(s)		2310004N10Rik; AI604795; D6Pas3; DNA segment, Chr 6, Pasteur Institute 3; FER1L1; LGMD2B; MMD1; RIKEN cDNA 2310004N10 gene; expressed sequence AI604795;
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. [MGI Ref ID J:149430] [MGI Ref ID J:149432] [MGI Ref ID J:92838]

Genotyping

Genotyping Information

Genotyping Protocols

Dysf^prmd, High Resolution Melting
Dysf^prmd, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Lostal W; Bartoli M; Bourg N; Roudaut C; Bentaib A; Miyake K; Guerchet N; Fougerousse F; McNeil P; Richard I. 2010. Efficient recovery of dysferlin deficiency by dual adeno-associated vector-mediated gene transfer. Hum Mol Genet :. [PubMed: 20154340]  [MGI Ref ID J:158933]

Additional References

Dysf^prmd related

Chase TH; Cox GA; Burzenski L; Foreman O; Shultz LD. 2009. Dysferlin deficiency and the development of cardiomyopathy in a mouse model of limb-girdle muscular dystrophy 2B. Am J Pathol 175(6):2299-308. [PubMed: 19875504]  [MGI Ref ID J:155340]

Concepcion D; Flores-Garcia L; Hamilton BA. 2009. Multipotent genetic suppression of retrotransposon-induced mutations by Nxf1 through fine-tuning of alternative splicing. PLoS Genet 5(5):e1000484. [PubMed: 19436707]  [MGI Ref ID J:149430]

Demonbreun AR; Fahrenbach JP; Deveaux K; Earley JU; Pytel P; McNally EM. 2011. Impaired muscle growth and response to insulin-like growth factor 1 in dysferlin-mediated muscular dystrophy. Hum Mol Genet 20(4):779-89. [PubMed: 21127009]  [MGI Ref ID J:168708]

Diaz-Manera J; Touvier T; Dellavalle A; Tonlorenzi R; Tedesco FS; Messina G; Meregalli M; Navarro C; Perani L; Bonfanti C; Illa I; Torrente Y; Cossu G. 2010. Partial dysferlin reconstitution by adult murine mesoangioblasts is sufficient for full functional recovery in a murine model of dysferlinopathy. Cell Death Dis 1:e61. [PubMed: 21364666]  [MGI Ref ID J:186461]

Farini A; Sitzia C; Navarro C; D'Antona G; Belicchi M; Parolini D; Del Fraro G; Razini P; Bottinelli R; Meregalli M; Torrente Y. 2012. Absence of T and B lymphocytes modulates dystrophic features in dysferlin deficient animal model. Exp Cell Res 318(10):1160-74. [PubMed: 22465227]  [MGI Ref ID J:186460]

Ho M; Post CM; Donahue LR; Lidov HG; Bronson RT; Goolsby H; Watkins SC; Cox GA; Brown RH Jr. 2004. Disruption of muscle membrane and phenotype divergence in two novel mouse models of dysferlin deficiency. Hum Mol Genet 13(18):1999-2010. [PubMed: 15254015]  [MGI Ref ID J:92838]

Laure L; Suel L; Roudaut C; Bourg N; Ouali A; Bartoli M; Richard I; Daniele N. 2009. Cardiac ankyrin repeat protein is a marker of skeletal muscle pathological remodelling. FEBS J 276(3):669-84. [PubMed: 19143834]  [MGI Ref ID J:147891]

Lostal W; Bartoli M; Roudaut C; Bourg N; Krahn M; Pryadkina M; Borel P; Suel L; Roche JA; Stockholm D; Bloch RJ; Levy N; Bashir R; Richard I. 2012. Lack of correlation between outcomes of membrane repair assay and correction of dystrophic changes in experimental therapeutic strategy in dysferlinopathy. PLoS One 7(5):e38036. [PubMed: 22666441]  [MGI Ref ID J:187293]

Millay DP; Maillet M; Roche JA; Sargent MA; McNally EM; Bloch RJ; Molkentin JD. 2009. Genetic manipulation of dysferlin expression in skeletal muscle: novel insights into muscular dystrophy. Am J Pathol 175(5):1817-23. [PubMed: 19834057]  [MGI Ref ID J:154690]

Nagaraju K; Rawat R; Veszelovszky E; Thapliyal R; Kesari A; Sparks S; Raben N; Plotz P; Hoffman EP. 2008. Dysferlin Deficiency Enhances Monocyte Phagocytosis: A Model for the Inflammatory Onset of Limb-Girdle Muscular Dystrophy 2B. Am J Pathol 172(3):774-785. [PubMed: 18276788]  [MGI Ref ID J:132272]

Roche JA; Lovering RM; Roche R; Ru LW; Reed PW; Bloch RJ. 2010. Extensive mononuclear infiltration and myogenesis characterize recovery of dysferlin-null skeletal muscle from contraction-induced injuries. Am J Physiol Cell Physiol 298(2):C298-312. [PubMed: 19923419]  [MGI Ref ID J:157507]

Spector I; Zilberstein Y; Lavy A; Genin O; Barzilai-Tutsch H; Bodanovsky A; Halevy O; Pines M. 2013. The involvement of collagen triple helix repeat containing 1 in muscular dystrophies. Am J Pathol 182(3):905-16. [PubMed: 23274062]  [MGI Ref ID J:193271]

Zhang Y; Maksakova IA; Gagnier L; van de Lagemaat LN; Mager DL. 2008. Genome-wide assessments reveal extremely high levels of polymorphism of two active families of mouse endogenous retroviral elements. PLoS Genet 4(2):e1000007. [PubMed: 18454193]  [MGI Ref ID J:149432]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

Colony Maintenance

Breeding & Husbandry	While maintaining a live colony, these mice are bred as homozygotes.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	Wild-type from the colony
	000664 C57BL/6J
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

See Terms of Use tab for General Terms and Conditions

The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX^® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX^® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX^® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.

---

Ordering Information
JAX^® Mice
Surgical and Preconditioning Services
JAX^® Services
Customer Services and Support
Tel: 1-800-422-6423 or 1-207-288-5845
Fax: 1-207-288-6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

Contact information

General inquiries regarding Terms of Use

Contracts Administration

phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice, Products & Services Conditions of Use

"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCTS" means biological materials supplied by JACKSON, and their derivatives. "RECIPIENT" means each recipient of MICE, PRODUCTS, or services provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than the internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE or PRODUCTS from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON's prior written authorization.

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of mice, products or services, JACKSON will, at its option, provide credit or replacement for the mice or product received or the services provided.

No Liability

In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS or services from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.

MICE and PRODUCTS are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or services. In addition, special terms and conditions of sale of certain MICE, PRODUCTS or services may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and services by JACKSON, and by its licensees and distributors.

Acceptance of delivery of MICE, PRODUCTS or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or services by JACKSON.