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Phenotypes Associated with This Genotype
Genotype
MGI:5695547
Allelic
Composition
Tg(NEFH-tTA)8Vle/0
Tg(tetO-TARDBP*)4Vle/0
Genetic
Background
involves: C3H/HeJ * C57BL/6J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(NEFH-tTA)8Vle mutation (3 available)
Tg(tetO-TARDBP*)4Vle mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
• significantly smaller brains are observed 8-10 weeks following Dox removal
• decreased cortical thickness beginning at 4 weeks following Dox removal
• brain atrophy is observed following Dox removal
• astrogliosis is observed 4 weeks after Dox removal
• denervation of neuromuscular junctions (NMJ) beginning 4 weeks after Dox removal
• by 6 weeks only 39.6% of NMJs are intact in tibialis anterior
• loss of endogenous nuclear mouse TARDBP+ 2-4 weeks following Dox removal
• accumulation of cytoplasmic ubiquitin with TARDBP+ inclusions occurs in brains and spinal cord
• 28% loss of lumbar motor neurons by 6 weeks following Dox removal; 50% loss by 8 weeks
• denervation of neuromuscular junctions (NMJ) beginning 4 weeks after Dox removal
• by 6 weeks only 39.6% of NMJs are intact in tibialis anterior
• accumulation of insoluble, phosphorylated cytoplasmic TARDBP+ inclusions in brain and spinal cord is detected as early as 1 week following Dox removal and reaches high levels by 4 weeks
• accumulation of insoluble TARDBP occurs prior to phosphorylation of protein
• inclusions are detected in motor cortex, striatum, visual and entorhinal, and somatosensory cortex, cerebellum and hippocampus
• inclusions are detected in fewer than 2% of spinal cord neurons
• by disease end stage 28% of neurons contain TARDBP+ puncta

behavior/neurological
• hindlimb clasping following Dox removal
• forelimb and/or hindlimb tremor following Dox removal
• progressive decline in balance as measured by accelerating rotarod occurs beginning 2 weeks after Dox removal
• progressive decline in coordinated movement as measured by accelerating rotarod occurs beginning 2 weeks after Dox removal
• progressive loss of grip strength as measured by wire hang test occurs beginning 2 weeks after Dox removal

mortality/aging
• mice die 10-18 weeks after removal of Dox; lifespan is extended if Dox is re-introduced
• median survival is 10.3 weeks off Dox

muscle
• decrease in mass of isolated tibialis anterior and gastrocnemius muscles following Dox removal

growth/size/body
• progressive weight loss beginning 2 weeks after Dox removal

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
amyotrophic lateral sclerosis type 10 DOID:0060201 OMIM:612069
J:225639


Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB), Gene Ontology (GO)
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last database update
10/12/2021
MGI 6.17
The Jackson Laboratory