Phenotypes Associated with This Genotype

Genotype
MGI:3722379

• Allelic Composition: Tg(Prnp-MAPT*P301L)JNPL3Hlmc/?
• Genetic Background: involves: C57BL/6 * DBA/2

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

mortality/aging

premature death ( J:63887 )

• within 3-4 weeks of phenotype onset, mice become moribund

growth/size/body

weight loss ( J:63887 )

• affected animals show decrease in body weight

cachexia ( J:63887 )

• observed in end-stage animals

behavior/neurological

decreased grooming behavior ( J:63887 )

• affected mice display reduction in grooming behavior

limb grasping ( J:63887 )

• at 4.5 months of age, F2 generation mice hold limbs in crossed position rather than extending them when lifted by the tail, and exhibit spontaneous back paw clenching while standing

• at 6.5 months of age, F1 generation mice hold limbs in crossed position rather than extending them when lifted by the tail, and exhibit spontaneous back paw clenching while standing

decreased grip strength ( J:63887 )

• affected mice fall after grasping rope briefly in hang tests

weakness ( J:63887 )

• after phenotype onset, weakness spreads to all limbs

• affected mice fall after grasping rope briefly in hang tests

abnormal posture ( J:63887 )

• after phenotype onset, mice exhibit dystonic posturing

abnormal locomotor behavior ( J:63887 )

• within 2 weeks of phenotype onset (occurring by 10 months of age), mice cannot ambulate

decreased vocalization ( J:63887 )

• affected mice display reduction in vocalization

nervous system

neurofibrillary tangles ( J:63887 )

• NFT are found in diencephalon, brainstem, cerebellar nuclei, and spinal cord, with 'pre-tangle' pathology observed in cortex neurons, hippocampus, and basal ganglia

gliosis ( J:63887 )

• fibrillary gliosis in anterior horns of spinal cord is seen

• gliosis occurs in brainstem, diencephalon, and basal telencephalon

decreased motor neuron number ( J:63887 )

• motor neuron counts in spinal cord are reduced ~48% from control values

abnormal cranial nerve morphology ( J:63887 )

• cranial nerve nuclei degeneration, including motor nucleus of trigemminal nerve and hypoglossal nerve is observed

muscle

abnormal sarcomere morphology ( J:63887 )

• sarcomeres are disorganized

abnormal skeletal muscle fiber morphology ( J:63887 )

• fibers are found in groups of small, acutely angled fibers, indicating neurogenic atrophy

• fibers have increased glycogen and lipofuscin, and redundant basement membranes

immune system

eye inflammation ( J:63887 )

• most mice develop eye irritation and have difficulty in opening their eyes

vision/eye

eye inflammation ( J:63887 )

• most mice develop eye irritation and have difficulty in opening their eyes

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
frontotemporal dementia		DOID:9255	OMIM:600274	J:63887