Phenotypes associated with this allele

• Allele Symbol: Grn^tm1.1Hiok
• Allele Name: targeted mutation 1.1, Hitoshi Okazawa
• Allele ID: MGI:6150889
• Summary: 1 genotype

Jump to	Allelic Composition	Genetic Background	Genotype ID
ht1	Grn^tm1.1Hiok/Grn^+	involves: C57BL/6J	MGI:6199038

Genotype
MGI:6199038

ht1

• Allelic Composition: Grn^tm1.1Hiok/Grn⁺
• Genetic Background: involves: C57BL/6J

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

behavior/neurological

impaired contextual conditioning behavior ( J:259943 )

♂ • in the fear-conditioning test, mice exhibit a decrease in total freezing time from 12 weeks of age

♂ • mice treated with vemurafenib, a B-Raf inhibitor, or a PKC-alpha inhibitor, Go6976, show recovery of cognitive function in the fear-conditioning test

impaired spatial learning ( J:308471 )

• increased latency to find platform in Morris water maze test from age 3 months

abnormal long-term spatial reference memory ( J:259943 )

♂ • in the Morris water maze test, 12 and 24 week old mice exhibit a decrease in time spent at the target region and a decrease in the number of target crossings, however latency to the platform does not differ

♂ • mice treated with vemurafenib, a B-Raf inhibitor, or a PKC-alpha inhibitor, Go6976, show recovery of memory in the Morris water maze

increased anxiety-related response ( J:308471 )

• less time spent in light in light-dark box test at age 12 months

impaired coordination ( J:259943 , J:308471 )

• reduced latency to fall (shorter time spent on rod) in rotarod test at age 12 months (J:308471)

♂ • rotarod abnormalities are not detected until 24 weeks of age (J:259943)

nervous system

decreased brain weight ( J:259943 )

• body weight is lower from birth until 16 weeks of age but recovers by 20 weeks of age

abnormal midbrain morphology ( J:308471 )

• cytoplasmic ubiquitinated TARDBP aggregates in midbrain from age 12 months

abnormal thalamus morphology ( J:308471 )

• cytoplasmic ubiquitinated TARDBP aggregates in thalamus from age 12 months

abnormal hippocampus morphology ( J:308471 )

• cytoplasmic ubiquitinated TARDBP aggregates in hippocampus from age 12 months

abnormal cerebral cortex morphology ( J:308471 )

• cytoplasmic ubiquitinated TARDBP aggregates in frontal association cortex and M2 motor cortex from age 6 months and dysgranular retrosplenial cortex from age 12 months

abnormal retrosplenial region morphology ( J:308471 )

• cytoplasmic ubiquitinated NUP62 aggregates in dysgranular retrosplenial cortex from age 12 months

abnormal frontal lobe morphology ( J:308471 )

• cytoplasmic ubiquitinated TARDBP aggregates in frontal association cortex from age 6 month

abnormal primary motor cortex morphology ( J:308471 )

• cytoplasmic ubiquitinated TARDBP aggregates in M2 motor cortex from age 6 months

decreased dendritic spine density ( J:259943 )

• 8 week old mice exhibit a reduction of dendritic spine density in layer 1 of frontal cortex, with an increase in spine elimination and a decrease in the abundance of stable spines over 24 hours

• treatment with vemurafenib or Go6976 rescues the reduction in the number of spines

neuronal cytoplasmic inclusions ( J:259943 )

• cytoplasmic aggregation of TDP43 from 24 weeks of age

• proportions of neurons with TDP43+ and Ub+ cytoplasmic aggregates increases over time, especially in the cerebral cortex

nervous system inclusion bodies ( J:259943 )

• mice exhibit cytoplasmic inclusion bodies from 24 weeks of age

• mice exhibit lentiform intranuclear inclusions from 24 weeks of age

tau protein deposits ( J:259943 )

• tau phosphorylation at Ser203 and mislocalization of tau to dendritic spines

cellular

abnormal endoplasmic reticulum morphology ( J:308471 )

• ER expansion in cortical neurons

abnormal cell cycle checkpoint function ( J:308471 )

• delayed or arrested G1/S transition in embryonic neural stem cells (NSCs) from cerebral cortex of E15 embryos

cellular necrosis ( J:308471 )

• early-stage transcriptional repression-induced atypical cell death (TRIAD) necrosis of neurons in cerebral cortex from ages 1 to 12 months, peaking at 3 months

growth/size/body

decreased body weight ( J:259943 )

• brain weight is slightly lower

increased body weight ( J:308471 )

• heavier from age 6 months

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Grn-related frontotemporal lobar degeneration with Tdp43 inclusions		DOID:0060672	OMIM:607485	J:259943