Phenotypes Associated with This Genotype

Genotype
MGI:3699325

• Allelic Composition: Grid2^tm1Mim/Grid2^tm1Mim
• Genetic Background: involves: C57BL/6 * CBA

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

behavior/neurological

abnormal motor coordination/balance ( J:24975 )

impaired righting response ( J:36182 )

• mice are slower to assume a swimming posture when dropped into water by a roll rotation load

• following injection of sodium arsanilate into the right middle ear mice show a slower recovery of the righting response with some mice unable to stop rotation even 28 days after injection

ataxia ( J:24975 )

• moderate locomotor ataxia is noticed by P12

impaired coordination ( J:24975 )

• in a running along an elevated runway task, homozygotes walk slowly along the runway with many slips, unlike wild-type mice that quickly run through with few slips; there is some improvement over time

• in a rotating rod task, the retention time of homozygotes is much shorter, although some improvement occurs over time

head tilt ( J:36182 )

• following injection of sodium arsanilate into the right middle ear mice show a more severe head tilt compared to controls

• prior to sodium arsanilate injection no head tilt is seen

abnormal locomotor activation ( J:24975 )

abnormal gait ( J:24975 )

• often walk with tottering steps and sometimes scramble to their hindlimbs

decreased vertical activity ( J:24975 )

• when rearing, homozygotes often pitch and roll due to poor balance

• total rearing time is shorter than that of wild-type

decreased locomotor activity ( J:24975 )

• at P26-28, show significantly reduced horizontal activity measured as total walking distances

• show a significant difference in total running time with high speeds

nervous system

abnormal cerebellum morphology ( J:73385 )

abnormal Purkinje cell morphology ( J:24975 )

• synaptic contacts with postsynaptic densities are sparse on the dendritic spines of Purkinje cells and correspondingly, spines without synaptic contacts but surrounded by sheets of Bergmann glial cells are more abundant than in wild-type

abnormal cerebellar molecular layer ( J:73385 )

• climbing fibers extend up to a more superficial regions of the molecular layer

thin cerebellar molecular layer ( J:73385 )

abnormal Purkinje cell innervation ( J:73385 , J:24975 )

• most cells are innervated by multiple climbing fibers (J:73385)

• climbing fibers innervate more distal portions of the Purkinje cells (J:73385)

• exhibit multiple innervation of Purkinje cells by climbing fibers (J:24975)

• some spines posses high electron density, like postsynaptic membranes, but miss the synaptic contact with parallel fibers, indicating that synapse formation between parallel fibers and Purkinje cells is impaired (J:24975)

abnormal CNS synapse formation ( J:24975 )

• synapse formation between parallel fibers and Purkinje cells is impaired

abnormal CNS synaptic transmission ( J:109764 , J:24975 )

• the amplitudes of Purkinje cell spontaneous compound post synaptic currents do not increase after conditioning stimulus unlike in wild-type controls indicating a failure of rebound potentiation (J:109764)

• direct depolarization of Purkinje cells also fails to induce rebound potentiation (J:109764)

• long-term depression of parallel fiber-Purkinje cell synaptic transmission is impaired, indicating impaired cerebellar LTD (J:24975)

abnormal GABA-mediated receptor currents ( J:109764 )

• results indicate GABAergic inhibition in the molecular layer is increased compared to wild-type controls

• bicuculline induced increase in the depolarized area is increased compared to wild-type controls

abnormal excitatory postsynaptic currents ( J:73385 )

• increase in the incidence of climbing fiber induced excitatory postsynaptic currents (CF-EPSCs) with more than one discrete step in mutant Purkinje cells compared to wild-type cells

• each CF-EPSC displays clear pair pulse depression to a similar or greater extent than that of wild-type currents

• Purkinje cells innervated by multiple climbing fibers display two populations of CF-EPSCs, one fast with a large amplitude (similar to wild-type) and one slow with a small amplitude (not seen in wild-type cells)

• slow CF-EPSCs become evident during the second postnatal week

increased miniature inhibitory postsynaptic current amplitude ( J:109764 )

• average mIPSC amplitude of Purkinje cells is increased compared to wild-type controls

• however, no difference is seen in isolated cultured Purkinje cells that lack climbing fiber innervation

absent long-term depression ( J:24477 )

• cultured Purkinje cells show slight potentiation under conditions that induce depression in cells from wild-type mice

homeostasis/metabolism

abnormal response to injury ( J:36182 )

• following injection of sodium arsanilate into the right middle ear mice show a more severe head tilt and slower recovery of the righting response compared to controls