Phenotypes Associated with This Genotype

Genotype
MGI:5308127

• Allelic Composition: Tg(Prnp-AR*112Q)#Deme/0
• Genetic Background: involves: C57BL/6 * SJL

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

behavior/neurological

limb grasping ( J:134789 )

• as early as 6 weeks of age, males exhibit intermittent clasping of the forelimbs, with frequency and severity of clasping increasing such that by 5 months of age, males develop full clasp, clutching all four limbs to the abdomen and curving the spine

• females develop intermittent forelimb clasping by 4 months of age which progresses to a full clasp by 16 months of age

• symptomatic 9-month old males that were castrated show milder clasping behavior than uncastrated mutant males

impaired coordination ( J:134789 )

• males show significant deficits on the rotarod at 3 months of age, which progresses such that by 8 months of age, males are unable to remain on the rod

• females show some deficits on the rotarod at 3 months of age but these are not consistent until 8 months age, and unlike males, females can still remain on the rotarod at 12 months of age, albeit for a shorter time

• symptomatic 9-month old males that were castrated show higher rotarod function than uncastrated mutant males, although still lower than in castrated wild-type mice

decreased grip strength ( J:134789 )

• 10 month old males exhibit a decrease in grip strength, for both all paws and forepaws alone

• females show decreased grip strength when tested for all paws

abnormal gait ( J:134789 )

• by 7 months of age, males exhibit abnormal gait characterized by low posture and widened stance in the hindlimbs and shorter waddling steps

• females do not exhibit gait abnormalities until 14 months of age

short stride length ( J:134789 )

• shorter waddling steps

decreased vertical activity ( J:134789 )

• males, but not females, show a decrease in vertical activity

• by 7 months of age, males are rarely seen rearing without leaning against the cage wall

decreased locomotor activity ( J:134789 )

• males, but not females, show a decrease in horizontal activity

paraparesis ( J:134789 )

• males exhibit hindlimb weakness

• however, mutants do not exhibit signs of muscle degeneration

growth/size/body

decreased body weight ( J:134789 )

• males stop gaining weight by 6 months of age and thus weigh less than controls by 8 months of age

nervous system

abnormal motor neuron morphology ( J:134789 )

• mutants develop a lower motor neuron disease characterized by slowly progressive hindlimb muscle weakne

• males show greater motor deficits and earlier disease onset than females

neuronal intranuclear inclusions ( J:134789 )

• neuronal intranuclear inclusions are seen in several regions of the brain, particularly in the cortex, brain stem, and the spinal cord

• progressive increase in size of neuronal intranuclear inclusions is seen in males

• females rarely exhibit neuronal intranuclear inclusions and only at more than 10 months of age

• symptomatic 9-month old males that were castrated show a reduced neuronal intranuclear inclusion load compared to uncastrated mutant males

reproductive system

reduced male fertility ( J:134789 )

♂ • decrease in male fertility

♂ • males become infertile after 6 months of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Kennedy's disease		DOID:0060161	OMIM:313200	J:134789