Phenotypes Associated with This Genotype

Genotype
MGI:5896835

• Allelic Composition: Tg(Thy1-UBQLN2*P497S)3Mont/?
• Genetic Background: involves: C3H * C57BL/6 * C57BL/6J

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

behavior/neurological

abnormal response to novel object ( J:239510 )

• mice do not discriminate between novel vs. familiar object as compared to controls

abnormal motor capabilities/coordination/movement ( J:239510 )

• progressive difficulty in movement

limb grasping ( J:239510 )

• forelimb and hindlimb clasping

impaired coordination ( J:239510 )

• progressive reduction in rotarod performance from 24 weeks of age

decreased grip strength ( J:239510 )

• progressive reduction in hindlimb grip strength from 6 weeks of age

• progressive reduction in forelimb grip strength from 24 weeks of age

hindlimb paralysis ( J:239510 )

• 10% of mice develop hindlimb paralysis

growth/size/body

decreased body weight ( J:239510 )

• reduction in body weight from 18-32 weeks as compared to controls

hematopoietic system

increased microglial cell activation ( J:239510 )

• Iba1 immunoreactivity is increased in 8 month old mice as compared to controls

immune system

increased microglial cell activation ( J:239510 )

• Iba1 immunoreactivity is increased in 8 month old mice as compared to controls

mortality/aging

premature death ( J:239510 )

• median survival is 305 days

muscle

abnormal skeletal muscle fiber morphology ( J:239510 )

• gastrocnemius muscle fibers are more triangular than rounded and are often surrounded by dark-stained nuclear bodies

decreased skeletal muscle fiber diameter ( J:239510 )

• smaller muscle fiber diameter in gastrocnemius muscle is observed in end stage (8 month) mice

muscle degeneration ( J:239510 )

• muscle wasting gastrocneumius muscle

nervous system

increased microglial cell activation ( J:239510 )

• Iba1 immunoreactivity is increased in 8 month old mice as compared to controls

loss of hippocampal neurons ( J:239510 )

• 40% reduction in neurons in dentate gyrus and CA1 regions in 8 month old mice

astrocytosis ( J:239510 )

• astrocytosis is observed in 8, but not 1, month old mice

abnormal innervation pattern to muscle ( J:239510 )

• denervation of end plates of neuromuscular junctions in the gastrocnemius muscle

decreased motor neuron number ( J:239510 )

• age-dependent loss of lower motor neurons from the ventral horn of the spinal cord

• however, little change in the number corticospinal motor neurons

abnormal axon morphology ( J:239510 )

• age-dependent reduction in large-caliber axons (L4) in end stage mice

nervous system inclusion bodies ( J:239510 )

• age dependent deposition of small and large size ubiquilin inclusions

• increased number of ubiquilin inclusions in hippocampus, spinal cord, and motor cortex as compared to Tg(Thy1-UBQLN2*P506T)6Mont transgenics

• ubiquilin inclusions appear prominent in layers V-VI of the cortex, the inner and middle molecular layers of the dentate gyrus, the the CA1 region of the hippocampus, the brainstem and striatum (many ubiquilin inclusions co-stain with ubiquitin)

• cytoplasmic TDP-43+ granular inclusions are observed in spinal motor neurons in 8 month old mice

• TDP-43+ inclusions are not observed in dentate gyrus of the hippocampus

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
amyotrophic lateral sclerosis type 15		DOID:0060206	OMIM:300857	J:239510