Mouse Genome Informatics
cx1
    Tg(CAG-GLVP)#Cath/0
Tg(GAL4-PABPN1*A16)#Cath/0

involves: C57BL/6 * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• 13% of mifepristone (MFP) treated mice to induce PABPN1 expression die suddenly around 10-12 weeks after the first MFP pellets are implanted
• more than 70% of mutants induced with MFP die or were euthanized within 10 months of induction and none survive beyond 12 months

behavior/neurological
• mutants induced with MFP exhibit reduced grooming behavior around 10-12 weeks after the first MFP pellets are implanted
• mutants induced with MFP exhibit impaired rotarod performance, falling off the rotarod much quicker than controls
• when MFP is withdrawn after 4 months of treatment, mice begin to show signs of behavioral improvement within 3-4 weeks of MFP withdrawal, with improved cage behavior and rotarod performance
• mutants induced with MFP exhibit reduced cage activity around 10-12 weeks after the first MFP pellets are implanted
• when MFP is withdrawn after 4 months of treatment, mice begin to show signs of behavioral improvement within 3-4 weeks of MFP withdrawal, with improved cage behavior

cardiovascular system
• MFP induced mice that die suddenly after 10-12 weeks of MFP treatment show dilated cardiomyopathy
• mutants induced with MFP develop dilated cardiomyopathy with disarray of cardiomyocytes, cellular infiltrates, and increased connective tissue; cardiac enlargement is seen as early as 3 months after induction

muscle
• MFP induced mice that die suddenly after 10-12 weeks of MFP treatment show dilated cardiomyopathy
• mutants induced with MFP develop dilated cardiomyopathy with disarray of cardiomyocytes, cellular infiltrates, and increased connective tissue; cardiac enlargement is seen as early as 3 months after induction
• MFP induced mutants exhibit muscles with internal nuclei, variability of muscle fiber size, increased connective tissue, rimmed vacuoles in cytoplasm of some muscle fibers and atrophy of muscle fibers after 6 months of induction
• MFP induced mutants show abnormally enlarged myonuclei containing clear zones within the nucleoplasm and large nuclear collections of filamentous structures that do not form well defined palisades or tangles
• in MFP induced mutants after 6 months of induction
• in MFP induced mutants after 6 months of induction
• mice implanted with subcutaneous timed-release of MFP pellets to induce PABPN1 expression, develop progressive non-necrotic myopathy associated with rimmed vacuoles and myonuclear filamentous inclusions
• MFP induced mutants develop muscle disease that is widespread with the involvement of pharyngeal, diaphragm, paraspinal, and limb muscles

skeleton
• mutants induced with MFP develop thoracic spine kyphosis

Mouse Models of Human Disease
OMIM IDRef(s)
Oculopharyngeal Muscular Dystrophy; OPMD 164300 J:178541