Phenotypes Associated with This Genotype

Genotype
MGI:5689841

• Allelic Composition: Tg(Thy1-TARDBP*)BOddo/Tg(Thy1-TARDBP*)BOddo
• Genetic Background: C57BL/6-Tg(Thy1-TARDBP*)BOddo

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

behavior/neurological

impaired spatial learning ( J:223932 )

• 15 month old mice perform worse than wild-type mice on the Morris water maze on day 2-5, traveling longer distances to find the hidden platform, showing fewer platform location crosses and spending less time in the target quadrant

abnormal long-term spatial reference memory ( J:223932 )

• 15 month old homozygotes perform worse than wild-type or hemizygotes in the radial arm water maze showing more entries in arms without platform on day 2, indicating impaired spatial memory

abnormal spatial working memory ( J:223932 )

• 15 month old mutants show fewer number of re-entries in the same arm of the radial arm water maze during each single trial, indicating impaired working memory

impaired coordination ( J:223932 )

• 15 month old homozygotes perform worse than wild-type controls or hemizygotes on the rotarod and on the accelerated rotarod

cellular

abnormal autophagy ( J:223932 )

• marker analysis indicates that autophagy induction is reduced in 15 month old mutants

homeostasis/metabolism

abnormal autophagy ( J:223932 )

• marker analysis indicates that autophagy induction is reduced in 15 month old mutants

abnormal enzyme/coenzyme activity ( J:223932 )

• 15 month old homozygotes show a decrease in chymotrypsin-like, trypsin-like, and caspase-like activities of the proteasome in the brain, indicating a decrease in proteasome function

nervous system

abnormal brain morphology ( J:223932 )

• mice show increased soluble levels of the 25 kDa C-terminal fragment of TARDBP in the nucleus and cytosol

• mice show rare cytosolic TARDBP (TDP-43) deposits

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
amyotrophic lateral sclerosis type 10		DOID:0060201	OMIM:612069	J:223932
Grn-related frontotemporal lobar degeneration with Tdp43 inclusions		DOID:0060672	OMIM:607485	J:223932