Phenotypes Associated with This Genotype

Genotype
MGI:5314754

• Allelic Composition: Tg(CAG-GLVP)#Cath/0; Tg(GAL4-PABPN1*A16)#Cath/0
• Genetic Background: involves: C57BL/6 * FVB

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

mortality/aging

premature death ( J:178541 )

• 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

decreased grooming behavior ( J:178541 )

• mutants induced with MFP exhibit reduced grooming behavior around 10-12 weeks after the first MFP pellets are implanted

impaired coordination ( J:178541 )

• 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• when MFP is withdrawn after 4 months of treatment, mice begin to show signs of behavioral improvement within 3-4 weeks of MFP withdrawal, with improved cage behavior and rotarod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

decreased locomotor activity ( J:178541 )

• 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• when MFP is withdrawn after 4 months of treatment, mice begin to show signs of behavioral improvement within 3-4 weeks of MFP withdrawal, with improved cage behavior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

dilated cardiomyopathy ( J:178541 )

• 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

dilated cardiomyopathy ( J:178541 )

• 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

abnormal muscle fiber morphology ( J:178541 )

• 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

skeletal muscle fiber atrophy ( J:178541 )

• in MFP induced mutants after 6 months of induction

increased variability of skeletal muscle fiber size ( J:178541 )

• in MFP induced mutants after 6 months of induction

myopathy ( J:178541 )

• 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

kyphosis ( J:178541 )

• mutants induced with MFP develop thoracic spine kyphosis

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
oculopharyngeal muscular dystrophy		DOID:11719	OMIM:164300	J:178541