Phenotypes Associated with This Genotype

Genotype
MGI:4412280

• Allelic Composition: Prnp^tm2Lnq/Prnp^tm2Lnq
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6N

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

Reactive gliosis in Prnp^tm3Lnq/Prnp^tm3Lnq (CJD) brain and neurodegeneration and dilated ventricles in Prnp^tm2Lnq/Prnp^tm2Lnq (FFI) brain

nervous system

increased neuron apoptosis ( J:200974 )

• signs of programmed cell death are seen in the thalamus

abnormal neuron proliferation ( J:200974 )

• markers of proliferating neurons are detected in the thalamus and superior colliculus

abnormal nervous system morphology ( J:154937 )

• mice develop profound neuropathology

enlarged brain ventricles ( J:154937 , J:200974 )

• at 16 and 20 months, brain ventricles are enlarged compared to in wild-type mice (J:154937)

• dilated ventricles (J:200974)

abnormal brain white matter morphology ( J:154937 )

• at 16 months, mice exhibit vacuolization and reactive gliosis in the deep white matter unlike in wild-type mice

abnormal thalamus morphology ( J:154937 , J:200974 )

• at 16 months, mice exhibit abnormal thalamus morphology (J:154937)

• at 18 months, mice exhibit neuronal loss in the thalamus unlike in wild-type mice (J:154937)

• numerous fibrillar deposits are seen that appear to be composed of prion protein (J:200974)

abnormal cerebral cortex morphology ( J:154937 )

• at 16 months, the motor cortex is flattened or concave unlike in wild-type mice

cerebellum atrophy ( J:154937 )

• at 16 months, mice exhibit cerebellum atrophy unlike wild-type mice

brain vacuoles ( J:154937 )

• in the deep white matter at 16 months

gliosis ( J:154937 )

• in the deep white matter at 16 months

decreased neuron number ( J:154937 )

• mice have fewer thalamic neurons compared with wild-type mice

neurodegeneration ( J:154937 )

neuron degeneration ( J:154937 , J:200974 )

• at 18 months mice exhibit loss of neurons in the thalamus unlike wild-type mice (J:154937)

• many disintegrating neurons are detected in the thalamus (J:200974)

behavior/neurological

abnormal behavior ( J:154937 )

impaired coordination ( J:200974 )

• performance on a rotarod improves in repeated trials but is slightly worse than controls

• in an automated mouse behavioral analysis assay, "cuddled hang" (time spent hanging from the ceiling) is strongly reduced

decreased vertical activity ( J:154937 )

• at night in mice 12 to 16 months old

decreased locomotor activity ( J:154937 )

• during the night, mice 12 to 16 months old spend less time traveling, travel less distance, and exhibit less jumping, hanging from cage tops, and rearing compared with wild-type mice

abnormal sleep duration ( J:200974 )

• spend more time at "rest" (correlate of sleep) in an automated mouse behavioral analysis assay

abnormal sleep pattern ( J:154937 )

• at early as 5 months of age, mice exhibit higher scores of awaken (activity that ends rest periods) and twitch (activity that disrupts rest periods) compared with wild-type mice

• by 16 months, mice exhibit periods of lying on the floor inactive during the night phase indicating exhaustion

immune system

immune system phenotype ( J:154937 )

N • mice are normally sensitive to hamster scrapie infection

homeostasis/metabolism

abnormal body temperature homeostasis ( J:154937 )

• mice exhibit a wider range in core body temperature than wild-type mice

cellular

increased neuron apoptosis ( J:200974 )

• signs of programmed cell death are seen in the thalamus

abnormal neuron proliferation ( J:200974 )

• markers of proliferating neurons are detected in the thalamus and superior colliculus

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
fatal familial insomnia		DOID:0050433	OMIM:600072	J:154937 , J:200974