Strain Name: |
B6.Cg-Tg(ACTA1-MYOT*T57I)71Mah/J |
|---|---|
Stock Number: |
006615 |
Availability: | Repository- Live |
General Terms and Conditions |
| Genes & Alleles | ACTA1; MYOT; Tg(ACTA1-MYOT*T57I)71Mah; |
Product Information
Strain Details
Type JAX® GEMM® Strain - Congenic Additional information on JAX® GEMM® Strains. Type JAX® GEMM® Strain - Mutant Strain Type JAX® GEMM® Strain - Transgenic Mating System +/+ sibling x Hemizygote (Female x Male) Species laboratory mouse Donating Investigator Michael Hauser, Duke University Medical Center Generation N10+F1 (28-DEC-07) Strain Description
Mice hemizygous for this TgT57I transgene are viable and fertile, with expression of a mutant form of human myotilin (MYOT harboring a T57I point mutation) directed by the human skeletal muscle alpha 1 actin (ACTA1) promoter. RT-PCR reveals transgene expression is specific to skeletal muscle. Mutant mice exhibit progressive muscle pathology. Small myofibrillar aggregates are observed in 2 week old mutant transgenic mice. By age 12 months, aggregates are predominantly found in the quadriceps and triceps (upper forelimb and hindlimb muscles), with the number of affected fibers and pathology increasing with age. Sarcolemmal damage is also observed. Fibrosis, tubular aggregation and adipose infiltration is observed in older transgenic mice. Muscle tissue of the diaphragm, soleus, biceps and ulnar do not form aggregates. Ultrastructural examination of muscle tissue from transgenic mice reveals sarcomeric abnormalities, such as Z-disc streaming. Isolated whole intact extensor digitorum longus muscle exhibits contractile dysfunction with reduced muscle mass and diminished specific maximum force. These mice recapitulate key features of human myotilinopathies and provide a model for studying the underlying mechanism of rela ted diseases such as limb-girdle muscular dystrophy type 1A (LGMD1A), myofibrillar myopathy (MFM), and spheroid body myopathy (SBM). Analysis of transgene inheritance patterns at The Jackson Laboratory colony and the donating investigator's colony suggest that the transgene integrated on the X chromosome. The effects (if any) of X chromosome inactivation in female hemizygotes are not yet characterized (October 2007).Strain Development
A transgenic construct containing the human myotilin gene, MYOT with a T57I point mutation, a c-myc (Myc) epitope tag, and SV40 polyadenylation site sequence under the control of the human skeletal muscle alpha 1 actin, ACTA1, promoter was injected into fertilized B6SJLF2 mouse eggs. Founder line 71 was established. Founder animals were backcrossed onto the C57BL/6J background for 9 generations by the donating investigator. Analysis of transgene inheritance patterns at The Jackson Laboratory colony and the donating investigator's colony suggest that the transgene integrated on the X chromosome (October 2007).
Related Disease (OMIM) Terms |
Mammalian Phenotype Terms assigned by genotype |
Gene & Allele Details
| Allele Symbol | Tg(ACTA1-MYOT*T57I)71Mah | ||
|---|---|---|---|
| Allele Name | transgene insertion 71, Michael Hauser | ||
| Common Name(s) | Tg(ACTA1-MYOT)71Mah; Tg(HSA-MYOT)71Mah; TgT57I; | ||
| Mutation Made By | Sean Garvey, Duke University Medical Center | ||
| Strain of Origin | (C57BL/6 x SJL)F2 | ||
| Expressed Gene | MYOT, myotilin, human | ||
| Promoter | ACTA1, actin, alpha 1, skeletal muscle, human | ||
| Molecular Note | The point mutation responsible for limb-girdle muscular dystrophy type 1A (LGMD1A) in a North American family - substitution of threonine for isoleucine at amino acid position 57 (T57I) of the protein - was introduced into the human myotilin cDNA. This mutant cDNA, comprising 1530 bp of coding sequence, 281 bp of 5' UTR and 485 bp of 3' UTR, with sequence encoding a MYC epitope tag inserted at the beginning of the coding region, was cloned into the HAS-VP1 expression vector downstream of nucleotides -2139 through +239 of the human actin, skeletal, alpha 1 gene followed by the splice acceptor from the SV40 P1 intron; two copies of the SV40 polyadenylation signal follow the 3'UTR of the cDNA. RT-PCR analysis of several tissues detected transgene-derived mRNA only in skeletal muscle, and immunoblot analysis with antibody against MYC demonstrated appropriate expression of the transgene product in multiple striated muscles. Immunohistologic examination of muscle sections revealed uniformity of expression in fibers within a muscle group and similarity of expression in slow, type I and in fast, type II fibers. Expression of the mutant human myotilin is 2.6-fold that of the endogenous mouse protein. [MGI Ref ID J:110377] | ||
Control Information
| Control | ||
|---|---|---|
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
Genotyping Protocols
Tg(ACTA1-MYOT*T57I)71Mah
Colony Maintenance
| Breeding & Husbandry | When maintaining a live colony, these mice are bred as hemizygotes. Analysis of transgene inheritance patterns at The Jackson Laboratory colony and the donating investigator's colony suggest that the transgene integrated on the X chromosome (October 2007). |
|---|---|
| Diet Information | LabDiet® 5K52/5K67 |
Related Strains
Strains carrying other alleles of ACTA1
View Strains carrying other alleles of ACTA1 (7 strains)
006612 B6.Cg-Tg(ACTA1-MYOT)12Mah/J
Additional Web Information
Congenic Nomenclature
Animal Health Reports
Room Number AX11
Research Applications
This mouse can be used to support research in many areas including:
Mouse/Human Gene Homologs
muscular dystrophy, limb-girdle
References
Selected Reference(s)
Garvey SM; Miller SE; Claflin DR; Faulkner JA; Hauser MA. 2006. Transgenic mice expressing the myotilin T57I mutation unite the pathology associated with LGMD1A and MFM. Hum Mol Genet 15(15):2348-2362. [PubMed: 16801328] [MGI Ref ID J:110377]
Price and Supply Information
| Strain Name: | B6.Cg-Tg(ACTA1-MYOT*T57I)71Mah/J |
| Stock Number: | 006615 |
Price Details
IMPORTANT NOTE: Prices are based on shipping destination. To view prices, select your shipping destination.
*NO Shipping Destination selected!
Supply Details
| Standard Supply | Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement. |
|---|---|
| Supply Notes |
Usually shipped between four and eight weeks of age. This strain is included in the Induced Mutant Resource Colony collection. |
| Licensing | See General Terms and Conditions below |
| Control Information | View Control Information in Strain Details. |
General Terms and Conditions
View JAX® Mice & Services Conditions of Use.
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 and Purchasing Information
Purchasing Information
JAX® Mice Orders
Surgical Services
Contact Information
Orders & Technical Support
Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
Technical Support Email Form