FVB-Tg(ACTA1-PABPN1*A17)1Drub/DrubJ

Stock number: 016193
Research areas: Neurobiology Research

Description

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.

Detailed 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. This is the replacement line, obtained from the Donating Investigator, for FVB-Tg(ACTA1-PABPN1*A17)1Drub/J, Stock No. 006655.

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.

Allele

Symbol: Tg(ACTA1-PABPN1*A17)1Drub
Name: transgene insertion 1, David Rubinsztein
MGI accession ID: MGI:3693304
Generation method: Transgenic
Attributes: Inserted expressed sequence
Marker symbol: Tg(ACTA1-PABPN1*A17)1Drub
Marker name: transgene insertion 1, David Rubinsztein
Chromosome: UN
Strain of origin: FVB/N
Expressed genes: PABPN1,poly(A) binding protein nuclear 1,human
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.
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.