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| A17-1 transgenic mice develop progressive muscle degeneration and may be useful in studies of human Oculopharyngeal Muscular Dystrophy and in Muscular Dystrophy or Codon Reiteration Disease research. | |||||||||||||||
- Description
- Disease & phenotype
- Genes & alleles
- Genotyping
- Health & care
- References
- Pricing & purchasing
- Terms of use
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 Coisogenic; Mutant Strain; Transgenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Generation +pN1
Generation DefinitionsDonating Investigator Prof. David Rubinsztein, Cambridge Institute for Medical Research Description
Mice hemizygous for the transgenic insert are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities until roughly four months of age. At four months, hemizygotes develop a progressive muscle weakness (measured by grip strength, wire maneuver and vertical gripping tests), which progresses to late onset locomoter defects around nine months of age. At nine months mice cannot lift their own body weight. They drag their pelvis when walking. There is no difference in body weight or mortality up to 15 months of age compared to controls. Hemizygotes develop KCl-insoluble inclusions containing PABPN1 in the nuclei of skeletal muscle fibers with tubulo-filamentous ultrastructures. The proportion of myocte nuclei with aggregates increases with age. Significantly elevated numbers of TUNEL-positive myocyte nuclei can be found at six and 12 months. TUNEL staining is widely used as a cell-death marker in muscle diseases in mice and humans. Muscles of hemizygotes contain increased numbers of centrally located nuclei and vacuoles compared to controls, which reflects the regenerative processes that can result from muscular dystrophy. This strain may prove useful as a model of human Oculopharyngeal Muscular Dystrophy and in Muscular Dystrophy or Codon Reiteration Disease research.Development
A transgenic construct containing a human skeletal actin (HSA1) promoter upstream of a bovine poly-(A) binding protein nuclear 1 (PABPN1) with 17 alanines was injected into FVB donor eggs. The mice were maintained by breeding hemizygous males with non-carrier/wildtype sibling females. Upon arrival at The Jackson Laboratory, the mice were crossed to FVB/NJ (Stock No. 001800) at least once to establish the colony.
Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| Considerations for Choosing Controls | ||
Related Strains
Strains carrying Tg(ACTA1-PABPN1*A17)1Drub allele
006655 FVB-Tg(ACTA1-PABPN1*A17)1Drub/J View Strains carrying Tg(ACTA1-PABPN1*A17)1Drub (1 strain)
Phenotype
Phenotype Information
- Characteristics of this human disease are associated with transgenes and other mutation types in the mouse.
Oculopharyngeal Muscular Dystrophy; OPMD
assigned by genotype
Tg(ACTA1-PABPN1*A17)1Drub/0
involves: FVB/N
- behavior/neurological phenotype
- abnormal grip strength
- mutants display age-dependent decreases in grip strength compared to nontransgenic controls from 2-15 months of age (MGI Ref ID J:115642)
- in male mice treated with doxycycline (DOX) from 6 weeks of age, grip strength and vertical gripping is improved compared to nontreated transgenic mice (MGI Ref ID J:115642)
- abnormal locomotor activation
- mutants show reluctance to walk from ~9 months (MGI Ref ID J:115642)
- abnormal motor coordination/ balance
- muscle phenotype
- abnormal skeletal muscle fiber morphology
- proportion of myocyte nuclei with tubulo-filamentous ultrastructures and containing KCl-insoluble aggregates increases with age, compared to nontransgenic controls (MGI Ref ID J:115642)
- mutants have increased numbers of apoptotic myocyte nuclei compared to controls at 6-12 months (MGI Ref ID J:115642)
- musle has increased numbers vacuoules (MGI Ref ID J:115642)
- aggregate formation is decreased with DOX treatment and number of apoptotic nuclei is reduced (MGI Ref ID J:115642)
- centrally nucleated skeletal muscle fibers
- musle has increased numbers of centrally located nuclei (MGI Ref ID J:115642)
- muscle weakness (MGI Ref ID J:115642)
- progressive muscle weakness
- mutant display weakness assessed by grip strength, wire maneuver and vertical gripping , leading to locomotor deficits (MGI Ref ID J:115642)
This mouse can be used to support research in many areas including:
Neurobiology Research
Muscular Dystrophy
Genes & Alleles
Gene & Allele Information provided by MGI
| Allele Symbol | Tg(ACTA1-PABPN1*A17)1Drub | ||
|---|---|---|---|
| Allele Name | transgene insertion 1, David Rubinsztein | ||
| Allele Type | Transgenic (random, expressed) | ||
| Common Name(s) | A17-1; A17.1; | ||
| Strain of Origin | FVB/N | ||
| Expressed Gene | PABPN1, poly(A) binding protein, nuclear 1, human | ||
| Promoter | ACTA1, actin, alpha 1, skeletal muscle, human | ||
| General Note | Of two lines descended from founders with this transgenic construct, line A7-1 has a more severe phenotype, correlated with higher transgene expression levels, than line A7-2. | ||
| Molecular Note | The transgene contains the human skeletal actin promoter upstream of a mutant bovine cDNA with a series of CGC codons encoding a 17-amino acid polyalanine tract. [MGI Ref ID J:115642] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Tg(ACTA1-PABPN1*A17)1Drub, Standard PCR
Helpful Links
Genotyping resources and troubleshooting
References
References provided by MGI
Additional References
Tg(ACTA1-PABPN1*A17)1Drub relatedDavies JE; Rose C; Sarkar S; Rubinsztein DC. 2010. Cystamine suppresses polyalanine toxicity in a mouse model of oculopharyngeal muscular dystrophy. Sci Transl Med 2(34):34ra40. [PubMed: 20519718] [MGI Ref ID J:167874]
Davies JE; Rubinsztein DC. 2011. Over-expression of BCL2 rescues muscle weakness in a mouse model of oculopharyngeal muscular dystrophy. Hum Mol Genet 20(6):1154-63. [PubMed: 21199860] [MGI Ref ID J:168849]
Davies JE; Sarkar S; Rubinsztein DC. 2008. Wild-type PABPN1 is anti-apoptotic and reduces toxicity of the oculopharyngeal muscular dystrophy mutation. Hum Mol Genet 17(8):1097-108. [PubMed: 18178579] [MGI Ref ID J:133466]
Davies JE; Wang L; Garcia-Oroz L; Cook LJ; Vacher C; O'Donovan DG; Rubinsztein DC. 2005. Doxycycline attenuates and delays toxicity of the oculopharyngeal muscular dystrophy mutation in transgenic mice. Nat Med 11(6):672-7. [PubMed: 15864313] [MGI Ref ID J:115642]
Jenal M; Elkon R; Loayza-Puch F; van Haaften G; Kuhn U; Menzies FM; Oude Vrielink JA; Bos AJ; Drost J; Rooijers K; Rubinsztein DC; Agami R. 2012. The poly(A)-binding protein nuclear 1 suppresses alternative cleavage and polyadenylation sites. Cell 149(3):538-53. [PubMed: 22502866] [MGI Ref ID J:186206]
Trollet C; Anvar SY; Venema A; Hargreaves IP; Foster K; Vignaud A; Ferry A; Negroni E; Hourde C; Baraibar MA; 't Hoen PA; Davies JE; Rubinsztein DC; Heales SJ; Mouly V; van der Maarel SM; Butler-Browne G; Raz V; Dickson G. 2010. Molecular and phenotypic characterization of a mouse model of oculopharyngeal muscular dystrophy reveals severe muscular atrophy restricted to fast glycolytic fibres. Hum Mol Genet 19(11):2191-207. [PubMed: 20207626] [MGI Ref ID J:159693]
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 When maintaining a live colony, these mice can be bred as hemizygotes. The Donating Investigator has not attempted to make the strain homozygous. Onset of the progressive muscle weakness and locomotor deficit phenotype is at 4 months of age in hemizygous animals.
Pricing and Purchasing
Pricing, Supply Level & Notes, Controls
| Pricing for USA, Canada and Mexico shipping destinations |
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Cryopreserved
Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $1980.00 At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.
Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
Supply Notes
- Cryorecovery - Standard.
Progeny testing is not required.
The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.Cryorecovery to establish a Dedicated Supply for greater quantities of mice.
Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).
| Pricing for International shipping destinations |
|
Cryopreserved
Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $2574.00 At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.
Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
Supply Notes
- Cryorecovery - Standard.
Progeny testing is not required.
The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.Cryorecovery to establish a Dedicated Supply for greater quantities of mice.
Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).
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Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| Considerations for Choosing Controls | ||
| Control Pricing Information for Genetically Engineered Mutant Strains. | ||
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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
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