Phenotypes Associated with This Genotype

Genotype
MGI:5308055

• Allelic Composition: Tg(Prnp-TARDBP)3cPtrc/Tg(Prnp-TARDBP)3cPtrc
• Genetic Background: C57BL/6-Tg(Prnp-TARDBP)3cPtrc

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

mortality/aging

premature death ( J:163231 )

• mutants become moribound between 1 and 2 months of age

growth/size/body

decreased body weight ( J:163231 )

• body weight is reduced from 14 days of age onward

behavior/neurological

impaired righting response ( J:163231 )

• between 1 and 2 months of age, mutants are unable to right themselves

limb grasping ( J:163231 )

• mutants fail to show proper escape extension by splaying their hindlimbs upon elevation

tremors ( J:163231 )

• mutants exhibit body tremors by 21 days of age

• however, there is no evidence of muscle atrophy

abnormal gait ( J:163231 )

• mutants develop an aberrant "swimming" gait

• by 21 days of age, mutants have difficulty walking faster than 10 cm/s and recruiting their hindlimbs

nervous system

decreased brain weight ( J:163231 )

• brain weight is lower at 1 month of age

abnormal brainstem morphology ( J:163231 )

• in the brainstem, eosinphilic aggregates are found mostly within the pontine nuclei and midbrain tegmentum, including the red nucleus

abnormal red nucleus morphology ( J:163231 )

• eosinphilic aggregates

gliosis ( J:163231 )

• reactive gliosis is seen in the anterior horn of the spinal cord

astrocytosis ( J:163231 )

• reactive astrocytosis is seen in the gray matter of the spinal cord

abnormal motor neuron morphology ( J:163231 )

• mutants exhibit neuronal cytoplasmic eosinophilic aggregates in spinal motor neurons

• about 10% of neurons in the anterior horn of the spinal cord had eosinophilic aggregates, with fewer in the posterior horn and brainstem

• motoneuron eosinophilic aggregates are composed of abnormal mitochondrial clusters; mitochondria have features suggestive of degeneration, with decreased cristae and vacuoles within the mitochondrial matrix

neuron degeneration ( J:163231 )

• degenerating neurites, axons and neurons are seen in the spinal cord

abnormal spinal cord white matter morphology ( J:163231 )

• degenerating mitochondria, and autophagic vacuoles, are seen within swollen axons in the spinal cord white matter

axon degeneration ( J:163231 )

• in the spinal cord

demyelination ( J:163231 )

• vacuolization of myelin and myelin ovoids indicate myelin degeneration in anterolateral funiculi of the spinal cord

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
amyotrophic lateral sclerosis type 10		DOID:0060201	OMIM:612069	J:163231
Grn-related frontotemporal lobar degeneration with Tdp43 inclusions		DOID:0060672	OMIM:607485	J:163231