Phenotypes Associated with This Genotype

Genotype
MGI:3836993

• Allelic Composition: Tg(Prnp*D177N*M128V)A21Rchi/0
• Genetic Background: involves: C57BL/6 * CBA

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

mortality/aging

premature death ( J:142098 )

• mice die from neurological disease with a mean lifespan of 704 days

• the length of illness (mean day of onset until death) is 293 days

behavior/neurological

abnormal spatial working memory ( J:142098 )

• mice younger than 320 days (i.e. before ataxia occurs) make significantly more errors in an eight-arm radial maze over 10 training days than controls

• latency to complete the test is similar to controls demonstrating that the deficit is unrelated to motor abnormalities

limb grasping ( J:142098 )

• mice suffering form neurological disease tightly clasp hindlimbs upon lifting by tail

ataxia ( J:142098 )

• mice develop ataxia with extension of hindlimbs and unbalanced posture with an age of onset at 452 days

impaired balance ( J:142098 )

• mice develop ataxia with extension of hindlimbs and unbalanced posture with an age of onset at 452 days

impaired coordination ( J:142098 )

• the mean latency to fall for mice in a rotarod test is 100 seconds less than for controls

abnormal sleep pattern ( J:142098 )

• mice spend about 10-fold less time in REM sleep than controls during both light and dark phases

• mice also spend less time in non-REM sleep during the dark phase too

• however, the total time sleeping is not significantly different

nervous system

abnormal brain morphology ( J:142098 )

• protease resistant Prnp deposits are found in many parts of the brain in mice suffering from neurological disease

• Prnp deposits ranged from diffuse synaptic-type depositions prominent in the hippocampus to plaque-like depositions in the reticular thalamic nucleus, the corpus callosum, the external and internal capsule, the cingulated cortex, and the anterior commissure nuclei

• depositions do not contain amyloid fibrils

abnormal cerebellar granule cell morphology ( J:142098 )

• the endoplasmic reticulum of granule neurons is swollen and fragmented in mice prior to the onset of disease

• the transgenic Prnp protein localizes in the ER of these cells instead of in the plasma membrane like the endogenous protein

astrocytosis ( J:142098 )

• hypertrophy and proliferation of astrocytes are prominent adjacent to Prnp depositions

abnormal brain wave pattern ( J:142098 )

• EEG activity is characterized by bursts of polyphasic complexes lasting from 0.3 to 4.6 seconds

• the power frequency spectrum of the polyphasic complexes is 7-8 Hz

• polyphasic complexes occur during wake or sleep periods with similar frequency

• most mice also have abnormal ''sawtooth'' waves with a frequency to power spectrum that peak around 4 Hz

skeleton

kyphosis ( J:142098 )

• kyphosis occurs with the onset of ataxia

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Creutzfeldt-Jakob disease		DOID:11949	OMIM:123400	J:142098