Phenotypes Associated with This Genotype

Genotype
MGI:6278939

• Allelic Composition: Atp2b1^{Tg(Thy1-CHMP2B*)1Rene}/Atp2b1^{Tg(Thy1-CHMP2B*)1Rene}
• Genetic Background: involves: C57BL/6 * DBA/2 * FVB/N

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

mortality/aging

premature death ( J:237873 )

• median survival of 5.5 months compared to 26 months in wild-type

growth/size/body

decreased body weight ( J:237873 )

• mice fail to gain weight normally from 1 month of age on

behavior/neurological

abnormal exploration in a new environment ( J:237873 )

• mice exhibit atypical patterns of exploration characterized by frequent changes of direction and spend more time in the center of the open field

increased food intake ( J:237873 )

• mice eat more and spend more time visiting food pellets at 5 months of age than controls

low sweet preference ( J:237873 )

• mice exhibit a lower preference for 2% and 4% sucrose solution than controls

decreased anxiety-related response ( J:237873 )

• mice spend more time in the center of the open field

increased grooming behavior ( J:237873 )

• mice exhibit repetitive face and ear cleaning

impaired righting response ( J:237873 )

• 70% of mice show an altered righting reflex when placed on the back between 4 and 6 months of age

limb grasping ( J:237873 )

• mice are unable to extend their hindlimbs when held by the tail as early as 3 months of age

tremors ( J:237873 )

• mice develop tremors

impaired coordination ( J:237873 )

• on the accelerating rotarod, 3 month old mice show a 2/3 reduction of motor capacities

jerky movement ( J:237873 )

• mice develop twitches

weakness ( J:237873 )

• 3 month old mice show a 25% decrease of muscle strength

head tossing ( J:237873 )

• mice exhibit recurrent repetitive head flicking

abnormal gait ( J:237873 )

• mice progressively develop motor dysfunction and gait alterations

• mice show a change in footprint pattern, with a 60%, 49% and 60% decrease in footstep length, width, and diagonal, respectively

• mice exhibit an exaggerated spacing of hindlimb feet position and paw placement relative to the body axis, with changes becoming more pronounced with age

short stride length ( J:237873 )

• mice show a 60% decrease in footstep length

decreased vertical activity ( J:237873 )

• mice make fewer rearings but rearings occur mostly in the center of the arena

hindlimb paralysis ( J:237873 )

• mice eventually show progressive hindlimb paralysis associated with a severely stilted gait

increased stereotypic behavior ( J:237873 )

• all mice exhibit stereotypical behavior in their home cage at 4-6 months of age, including upright scrabbling, repetitive burying and relentless chewing of a piece of food

• mice exhibit recurrent repetitive head flicking, kangaroo-like position with mouse in up-right position sitting on its rear, and repetitive face and ear cleaning

increased vertical stereotypic behavior ( J:237873 )

• mice exhibit upright scrabbling (rearing along a wall or in a corner and appearing to run or climb in place) and recurrent kangaroo-like position with mouse in up-right position sitting on its rear

abnormal social investigation ( J:237873 )

• mice show a decrease of social interaction with their cage mates

muscle

abnormal muscle electrophysiology ( J:237873 )

• electromyography of resting activity in the gastrocnemius muscle shows abnormal spontaneous activity with fibrillation potentials when paralysis occurs and numerous fasciculations are seen, suggesting muscle denervation

muscle fasciculation ( J:237873 )

• electromyography of resting activity in the gastrocnemius muscles shows numerous fasciculations

nervous system

gliosis ( J:237873 )

• mice show a progressive age-dependent reactive gliosis

astrocytosis ( J:237873 )

• 6 month old mice exhibit astrogliosis in the cortex and spinal cord

• astrocytic activation is more pronounced than microglial activation

abnormal neuromuscular synapse morphology ( J:237873 )

• number of denervated or partially denervated neuromuscular junctions is 70% higher at 12 months than in wild-type littermates

neuronal cytoplasmic inclusions ( J:237873 )

• mice develop age-dependent cytoplasmic inclusions immunoreactive for p62 and ubiquitin

abnormal sciatic nerve morphology ( J:237873 )

• the proportion of large myelinated axons in the sciatic nerve is decreased while the number of small caliber myelinated axons is increased

• however, mice show normal numbers of motor neurons in the ventral horn of the spinal cord

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
frontotemporal dementia		DOID:9255	OMIM:600274	J:237873
frontotemporal dementia and/or amyotrophic lateral sclerosis 7		DOID:0111227	OMIM:600795	J:237873