Phenotypes associated with this allele

• Allele Symbol: Grid2^ts3
• Allele Name: ts3
• Allele ID: MGI:5751064
• Summary: 1 genotype

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Grid2^ts3/Grid2^ts3	C57BL/6J-Grid2^ts3	MGI:5779531

Genotype
MGI:5779531

hm1

• Allelic Composition: Grid2^ts3/Grid2^ts3
• Genetic Background: C57BL/6J-Grid2^ts3

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

Grid2^ts3/Grid2^ts3 mice fall frequently and display an inability to right themselves easily

growth/size/body

decreased body size ( J:222504 )

• ataxic mice are significantly smaller than control littermates

decreased body weight ( J:222504 )

• body weights of ataxic mice are significantly reduced at 4, 8, and 16 weeks of age

behavior/neurological

limb grasping ( J:222504 )

• frequent limb-clasping after 12 weeks of age

abnormal motor coordination/balance ( J:222504 )

• mice begin to fall frequently after weaning (3 weeks of age), most likely due to abnormal control of their hind limbs

impaired righting response ( J:222504 )

• mice display a difficulty to right themselves

ataxia ( J:222504 )

• rates of ataxic progression show individual variations

• mice develop a slowly progressive ataxia starting at ~3 weeks of age

• ataxic mice exhibit typical traits of paraplegia but no signs of spasticity

• some mice develop mild appendicular ataxia, including the fore limbs

impaired limb coordination ( J:222504 )

• at 6 weeks of age, mice begin to walk dragging their hind limbs

abnormal gait ( J:222504 )

• mice move their toes parallel to the direction of movement and do not attach their heels on the ground

short stride length ( J:222504 )

• mice exhibit a short-stepped gait

hindlimb paralysis ( J:222504 )

• hind limbs become entirely paralyzed in many cases

nervous system

abnormal Purkinje cell morphology ( J:222504 )

• EM revealed lipofuscin accumulation in Purkinje cell bodies, representing senescent postmitotic neurons at 30 weeks of age

abnormal Purkinje cell dendrite morphology ( J:222504 )

• mice show abnormal Purkinje cell dendrite branching and significantly thicker dendrites at 30 weeks of age

• dendritic spines are smaller and abnormally shaped; thin (filopodia-like or headed) spines are predominant indicating a deficit in spine maturation, while stubby or mushroom-shaped spines, typical of normal and mature PCs, are significantly decreased

• however, dendritic spine density is similar to that of wild-type controls

decreased Purkinje cell number ( J:222504 )

• average Purkinje cell number is significantly decreased in cerebellar lobules VII and VIII at 30 weeks of age

decreased cerebellar granule cell number ( J:222504 )

• mice show a significant reduction in granule cell density at 30 weeks of age

abnormal cerebellar molecular layer ( J:222504 )

• VGluT2-positive climbing fiber (CF) terminals are markedly increased in number and distributed throughout the full extent of the molecular layer, unlike in control mice where CF terminals are distributed along calbindin-stained Purkinje cell dendrites in the basal four-fifths of the molecular layer

abnormal cerebellum lobule morphology ( J:222504 )

• some mice exhibit significant atrophy of the anterior folia where the anterior part of the cerebellar folia is significantly smaller in size than its posterior counterpart; in other mutants, however, neither the anterior part nor the whole cerebella are smaller than those of controls

• average Purkinje cell number is significantly decreased in cerebellar lobules VII and VIII at 30 weeks of age

• however, cerebellar foliation, laminated organization, and monolayer alignment of Purkinje cells are normal

small cerebellum ( J:222504 )

• relative cerebellar size (cerebellum/cerebrum) is significantly smaller than that of control littermates

cerebellum atrophy ( J:222504 )

• all ataxic mice exhibit significant cerebellar atrophy, as shown by micro-MRI and histological analysis

• severity of cerebellar atrophy varies between individual mice

• however, the spinal cord and sciatic nerves appear morphologically normal at 4 months of age

abnormal CNS synapse formation ( J:222504 )

• affected mice show impaired parallel fiber- Purkinje cell (PF-PC) synapse formation in the cerebellum at 4 months of age

• ~17% of mutant synapses are mismatched i.e. the postsynaptic density of the PC spine is significantly longer than the active zone of the PF terminal

• ~40% of PC spines are "free" i.e. lacking synaptic contact with PF terminals

reproductive system

abnormal fertility/fecundity ( J:222504 )

• both male and female mutant mice fail to produce offspring under natural breeding conditions, likely due to ataxia