Phenotypes associated with this allele

• Allele Symbol: Grid2^tm1Mim
• Allele Name: targeted mutation 1, Masayoshi Mishina
• Allele ID: MGI:2178052
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Grid2^tm1Mim/Grid2^tm1Mim	B6.Cg-Grid2^tm1Mim	MGI:4943910
hm2	Grid2^tm1Mim/Grid2^tm1Mim	involves: C57BL/6 * CBA	MGI:3699325

Genotype
MGI:4943910

hm1

• Allelic Composition: Grid2^tm1Mim/Grid2^tm1Mim
• Genetic Background: B6.Cg-Grid2^tm1Mim

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

behavior/neurological

abnormal eye blink conditioning behavior ( J:89436 , J:107990 )

• reacquisition and retention of the conditioned response are also impaired (J:89436)

• mice are severely impaired with acquisition of the earlier, nonstartle component of response as well as of the adaptively timed response (J:89436)

• however, acquisition of the trace eye blink conditioning response is similar to controls (J:89436)

• acquisition of delay eye blink conditioning is severely impaired when the conditioned stimulus and unconditioned stimulus have temporal overlap but not when they don't overlap (J:107990)

abnormal reflex ( J:101081 )

abnormal optokinetic reflex ( J:101081 )

• exhibit significantly larger phase lag at all frequencies examined

• do not display OKR adaptation in response to continuous oscillation of a screen at 0.4 Hz +/- 1.8 degrees unlike wild-type mice

• flocculectomy does not significantly alter the abnormal OKR; however, lesions of the dorsal cap olivary nuclei neurons do reduce OKR abnormalities

abnormal vestibuloocular reflex ( J:101081 )

• exhibit higher VOR dark (VORD) gains, lower VOR light with earth stationary visual stimuli (VORL) gains and higher VOR light with synchronously moving visual stimuli (VORS) gains compared to wild-type mice

• exhibit higher VORD gains at the lowest amplitude tested with progressively lower gains as the angular amplitude of head rotation increases, the opposite of what is seen in wild-type or Grid2^Lc homozygous mice

• VORD phase differs from wild-type and Grid2^Lc homozygous mice at rotations frequencies higher and lower than 0.4 Hz

• VORS gains are larger to VORL gains, the opposite of what is seen in wild-type mice

• VOR gain is nearly constant across all conditions, regardless of the relationship between screen and head rotation, and lower than VORD gain, unlike in wild-type mice

• adaptive changes to VORD gains from training are not seen, unlike in wild-type mice

• flocculectomy does not significantly alter the abnormal VORD and VORL gains; however, lesions of the dorsal cap olivary nuclei neurons do reduce VOR abnormalities

impaired coordination ( J:97010 )

• fall off a stationary rod or rotarod earlier than wild-type controls and mice homozygous for Grid2^Lc

abnormal eye movement ( J:97010 , J:101081 )

• the eye moves irregularly and continuously (J:97010)

• spectral analysis detects spontaneous eye movement at low and high frequencies (J:97010)

• spontaneous eye movement is increased in both light and dark conditions although results indicate that visual inputs contribute to the increased movement (J:97010)

• bilateral flocculectomy decreased the fast component of spontaneous eye movement, abolished the peak around 10 Hz, and decreased the peak around 1 Hz in the power spectrum (J:97010)

• a correlation is seen between complex spikes and clustered firings and the spontaneous eye movement (J:97010)

• involuntary oscillatory eye movement (J:101081)

nervous system

abnormal action potential ( J:97010 )

• Purkinje cells sometimes show repetitive firing of apparent simple spikes with short intervals (clustered firing)

• time courses of complex spikes are variable

• autocorrelation histograms for apparent simple spikes show a peak at a very short lag time and multiple additional peaks

• the periodicity of about 10 Hz appears to be attributable to the clustered firings

• clustered firing is evoked by climbing fiber activation

• a correlation is seen between complex spikes and clustered firings and the spontaneous eye movement

increased prepulse inhibition ( J:89405 )

vision/eye

abnormal eye movement ( J:97010 , J:101081 )

• the eye moves irregularly and continuously (J:97010)

• spectral analysis detects spontaneous eye movement at low and high frequencies (J:97010)

• spontaneous eye movement is increased in both light and dark conditions although results indicate that visual inputs contribute to the increased movement (J:97010)

• bilateral flocculectomy decreased the fast component of spontaneous eye movement, abolished the peak around 10 Hz, and decreased the peak around 1 Hz in the power spectrum (J:97010)

• a correlation is seen between complex spikes and clustered firings and the spontaneous eye movement (J:97010)

• involuntary oscillatory eye movement (J:101081)

hearing/vestibular/ear

abnormal vestibuloocular reflex ( J:101081 )

• exhibit higher VOR dark (VORD) gains, lower VOR light with earth stationary visual stimuli (VORL) gains and higher VOR light with synchronously moving visual stimuli (VORS) gains compared to wild-type mice

• exhibit higher VORD gains at the lowest amplitude tested with progressively lower gains as the angular amplitude of head rotation increases, the opposite of what is seen in wild-type or Grid2^Lc homozygous mice

• VORD phase differs from wild-type and Grid2^Lc homozygous mice at rotations frequencies higher and lower than 0.4 Hz

• VORS gains are larger to VORL gains, the opposite of what is seen in wild-type mice

• VOR gain is nearly constant across all conditions, regardless of the relationship between screen and head rotation, and lower than VORD gain, unlike in wild-type mice

• adaptive changes to VORD gains from training are not seen, unlike in wild-type mice

• flocculectomy does not significantly alter the abnormal VORD and VORL gains; however, lesions of the dorsal cap olivary nuclei neurons do reduce VOR abnormalities

Genotype
MGI:3699325

hm2

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

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:24975 , 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)

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

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

abnormal CNS synapse formation ( J:24975 )

• synapse formation between parallel fibers and Purkinje cells is impaired

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

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

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