Phenotypes associated with this allele

• Allele Symbol: Grid2⁺
• Allele Name: wild type
• Allele ID: MGI:2430769
• Summary: 11 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
ht1	Grid2^Lc/Grid2^+	B6CBACa A^w-J/A-Grid2^Lc/J	MGI:3581157
ht2	Grid2^Lc-J/Grid2^+	BALB/cByJ-Grid2^Lc-J/+	MGI:3844321
ht3	Grid2^Lc-J/Grid2^+	involves: 129X1/SvJ * BALB/cByJ * C57BL/6	MGI:4360698
ht4	Grid2^Lc/Grid2^+	involves: C57BL/6 * CBA	MGI:4820961
ht5	Grid2^Lc/Grid2^+	involves: C57BL/6 * CBA/CaGnLe	MGI:4944053
ht6	Grid2^Lc/Grid2^+	involves: STOCK Mitf^Mi-wh	MGI:4441339
cn7	Cacna1a^tm1Kano/Cacna1a^tm1Kano Grid2^tm1(cre)Mwa/Grid2^+	involves: C57BL/6 * C57BL/6N	MGI:5140544
cn8	Cacna1a^tm1Kano/Cacna1a^tm1Kano Grid2^tm1(cre)Mwa/Grid2^+	involves: C57BL/6N	MGI:5307916
cx9	Grid2^Lc-J/Grid2^+ Trp53^tm1Tyj/Trp53^tm1Tyj	involves: 129S2/SvPas * 129X1/SvJ * BALB/cByJ * C57BL/6	MGI:4360675
cx10	Bax^tm1Sjk/Bax^tm1Sjk Grid2^Lc-J/Grid2^+	involves: 129X1/SvJ * BALB/cByJ * C57BL/6	MGI:4360653
cx11	Bax^tm1Sjk/Bax^+ Grid2^Lc-J/Grid2^+	involves: 129X1/SvJ * BALB/cByJ * C57BL/6	MGI:4360655

Genotype
MGI:3581157

ht1

• Allelic Composition: Grid2^Lc/Grid2⁺
• Genetic Background: B6CBACa A^w-J/A-Grid2^Lc/J

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

behavior/neurological

abnormal grooming behavior ( J:50315 )

• the number and duration of several grooming components (licking the forelimb, the abdomen, the back, and the hindlimb) is decreased compared to in wild-type mice

• however, the number and duration of body-shaking episodes is normal as is the serial organization of grooming

ataxia ( J:39109 )

• due to progressive loss of Purkinje cells

hearing/vestibular/ear

reduced linear vestibular evoked potential ( J:116914 )

• elevated threshold and reduced amplitudes

nervous system

Purkinje cell degeneration ( J:39109 )

• occurs within the first three weeks of life

Genotype
MGI:3844321

ht2

• Allelic Composition: Grid2^Lc-J/Grid2⁺
• Genetic Background: BALB/cByJ-Grid2^Lc-J/+

Pyknotic Purkinjie cells in Grid2^Lc-J/Grid2⁺ mouse cerebellum

behavior/neurological

ataxia ( J:42385 )

• first observed at 13 days of age

abnormal posture ( J:42385 )

• unable to maintain a rearing posture even when supported

titubation ( J:42385 )

• mice may show head but not body movement

abnormal gait ( J:42385 )

• apparent by 2 weeks of age

• mice intermittently sway and lurch forward

weaving ( J:42385 )

nervous system

abnormal cerebellar foliation ( J:42385 )

• hematoxylin and eosin staining of histological sections show significant degeneration of Purkinje cells in this area

Purkinje cell degeneration ( J:42385 )

• precedes appearance of ataxic gait

Genotype
MGI:4360698

ht3

• Allelic Composition: Grid2^Lc-J/Grid2⁺
• Genetic Background: involves: 129X1/SvJ * BALB/cByJ * C57BL/6

behavior/neurological

ataxia ( J:62117 )

• a swaying of the body and tendancy to fall from side to side is found in the third week of life and persists in the adult

nervous system

reduced cerebellar foliation ( J:62117 )

• sparsely populated, atrophic lobes

abnormal cerebellar Purkinje cell layer ( J:62117 )

• at 30 days of age there are only 6% of normal numbers of Purkinje cells and these are not aligned in a monolayer

abnormal Purkinje cell dendrite morphology ( J:62117 )

• the Purkinje cells have stunted, poorly developed dendritic trees that fail to reach the pial surface

decreased Purkinje cell number ( J:62117 )

abnormal cerebellar granule layer morphology ( J:62117 )

• the cerebellum has only 10% of normal numbers of granule cells at 30 days of age

cerebellum atrophy ( J:62117 )

• cerebellar atrophy is found by 30 days of age and persists

Genotype
MGI:4820961

ht4

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

behavior/neurological

decreased exploration in new environment ( J:107881 )

• mice exhibit reduced hole pokes and frequency of hole poking compared with wild-type mice

• however, walking time is normal and exploration is normally decreased by cerebellectomization

hyperactivity ( J:107881 )

• mice exhibit increased spontaneous activity compared with wild-type mice

homeostasis/metabolism

increased circulating corticosterone level ( J:44206 )

• after 15 minutes, LPS-stressed mice exhibit a 1.8-fold increase in plasma corticosterone levels compared with similarly treated wild-type mice

• mice exposed to a novel environment exhibit a 2-fold increased corticosterone levels compared with similarly wild-type mice

• a IL1 receptor antagonist-treated mice treated with LPS or exposed to novelty exhibit increased corticosterone levels compared with similarly treated wild-type mice

• pre-treatment with corticotropin-releasing hormone attenuates the abnormal surge in corticosterone levels

• however, basal corticosterone levels are normal

increased circulating adrenocorticotropin level ( J:44206 )

• after 15 minutes, LPS-stressed mice exhibit an 8-fold increase in plasma adrenocorticotropin (ACTH) levels compared with similarly treated wild-type mice

• mice exposed to a novel environment exhibit a 3.5-fold increased ACTH levels compared with similarly wild-type mice

• a IL1 receptor antagonist-treated mice treated with LPS or exposed to novelty exhibit increased ACTH levels compared with similarly treated wild-type mice

• pre-treatment with corticotropin-releasing hormone attenuates the abnormal surge in ACTH levels

• however, basal ACTH levels are normal

Genotype
MGI:4944053

ht5

• Allelic Composition: Grid2^Lc/Grid2⁺
• Genetic Background: involves: C57BL/6 * CBA/CaGnLe

behavior/neurological

abnormal optokinetic reflex ( J:101081 )

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

abnormal vestibuloocular reflex ( J:101081 )

• exhibit higher VOR dark (VORD) gains

• VORD phase differs from wild-type and Grid2 ^tm1Mim homozygous mice at rotations frequencies higher and lower than 0.4 Hz

• increases in VOR light with synchronously moving visual stimuli (VORS) gains at high frequencies or high amplitudes are larger than in wild-type controls

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

hearing/vestibular/ear

abnormal vestibuloocular reflex ( J:101081 )

• exhibit higher VOR dark (VORD) gains

• VORD phase differs from wild-type and Grid2 ^tm1Mim homozygous mice at rotations frequencies higher and lower than 0.4 Hz

• increases in VOR light with synchronously moving visual stimuli (VORS) gains at high frequencies or high amplitudes are larger than in wild-type controls

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

Genotype
MGI:4441339

ht6

• Allelic Composition: Grid2^Lc/Grid2⁺
• Genetic Background: involves: STOCK Mitf^Mi-wh

behavior/neurological

abnormal discrimination learning ( J:13161 )

• mice exhibit impaired visual discrimination learning in a water escape test compared with wild-type mice

abnormal spatial learning ( J:30686 )

• mice exhibit impaired spatial learning in a Z-maze filled with water compared with wild-type mice

abnormal motor coordination/balance ( J:158918 )

• in an Erasmus ladder test step time and overall walking pattern are abnormal

ataxia ( J:158918 )

impaired coordination ( J:158918 )

• decrease in latency to fall of a rotarod

nervous system

abnormal cochlear VIII nucleus morphology ( J:121314 )

• loss of cartwheel cells in the dorsal cochlear nucleus

decreased Purkinje cell number ( J:121314 )

• Purkinje cell loss

Genotype
MGI:5140544

cn7

• Allelic Composition: Cacna1a^tm1Kano/Cacna1a^tm1Kano; Grid2^tm1(cre)Mwa/Grid2⁺
• Genetic Background: involves: C57BL/6 * C57BL/6N

nervous system

abnormal neuron morphology ( J:173318 )

• regression of surplus climbing fibers (CFs) is severely impaired compared to in control mice

• from P5 to P7, the bias toward strengthening single CFs is impaired compared to in control mice

• multiple CFs translocate to dendrites and impairs elimination of CF synapses from the soma unlike in control cells

abnormal CNS synaptic transmission ( J:173318 )

• at P5 to P6, Purkinje cells (PCs) in cerebellar slices exhibit reduced calcium currents compared with control cells

• PCs lack P/Q-type voltage-dependent calcium channel (VDCC) compared with control cells

• climbing fiber (CF)-induced calcium transients in PCs are reduced compared to in control cells

• however, mice exhibit normal P/Q channel contribution to CF to PC synaptic transmission and spontaneous inhibitory postsynaptic currents at P6 to P7 and P10

abnormal excitatory postsynaptic currents ( J:173318 )

• from P5 to P8, the fractions of multiple CF-EPSCs remains unchanged unlike in control mice

prolonged excitatory postsynaptic current decay time ( J:173318 )

• in climbing fiber cells

prolonged excitatory postsynaptic current rise time ( J:173318 )

• in climbing fiber cells

Genotype
MGI:5307916

cn8

• Allelic Composition: Cacna1a^tm1Kano/Cacna1a^tm1Kano; Grid2^tm1(cre)Mwa/Grid2⁺
• Genetic Background: involves: C57BL/6N

nervous system

abnormal Purkinje cell morphology ( J:180582 )

• soma surface of Purkinje cells (PCs) is rough in contrast to smooth surface in controls

Purkinje cell degeneration ( J:180582 )

• Purkinje cell (PC) numbers decrease starting at P21 and continue to decrease; soma and dendrites of PCs show degenerative features like somatic shrinkage, darkened cytoplasm, increased electron-dense materials and accumulation of mitochondria with few soma or dendrites found in the cerebellar cortex by P35

• PC degeneration is more apparent in anterior lobules than posterior lobules; remaining PCs display striped or banded patterns

abnormal Purkinje cell dendrite morphology ( J:180582 )

• surface of Purkinje cell dendrites is rough with protrusion of spines or spine-like processes that form asymmetrical synapses with nerve terminals

• number of spines per 1 um of dendrites (>2 um in caliber) is significantly increased compared to controls

abnormal cerebellar molecular layer ( J:180582 )

• terminal profiles in the neuropil are enlarged and in contact with multiple Purkinje cell (PC) spines, often engulfing them, resulting in highly convoluted terminal contours; however density of asymmetrical synapses on PCs is significantly decreased relative to controls

• parallel fiber (PF) terminals are sparse, with many appearing coarse and intense on basis of Slc17a7 (VGluT1) immunolabeling; some PF-PC synapses show a 1:1 contact between PF terminals and PC spines but other exhibit large PF terminals forming multiple contacts

• climbing fiber (CF) terminals are irregular in shape and size; innervation stops midway along proximal dendrites; number of perisomatic CF terminals per unit area of somatic surface is markedly higher than in controls on basis of Slc17a6 (VGluT2) immunolabeling

• regressed innervation territory of climbing fibers on Purkinje cells down to basal dendrites and somata is observed in mutants resulting in multiple innervation

small cerebellum ( J:180582 )

• cerebellum is smaller than in controls at P21, but foliation and laminar organization as well as dendritic branching appear normal

• cerebellum size is reduced even more from P21 to adult

abnormal excitatory postsynaptic current amplitude ( J:180582 )

• unitary EPSCs fromPurkinje cells have larger and more variable amplitudes than controls

increased neurotransmitter release ( J:180582 )

• paired-pulse ratio at short interpulse intervals is smaller than in controls indicating a higher presynaptic release probability

Genotype
MGI:4360675

cx9

• Allelic Composition: Grid2^Lc-J/Grid2⁺; Trp53^tm1Tyj/Trp53^tm1Tyj
• Genetic Background: involves: 129S2/SvPas * 129X1/SvJ * BALB/cByJ * C57BL/6

behavior/neurological

ataxia ( J:62117 )

• disruption of Trp53 does not prevent or change the onset of the lurcher ataxia, which is found in the thrid week of life

Genotype
MGI:4360653

cx10

• Allelic Composition: Bax^tm1Sjk/Bax^tm1Sjk; Grid2^Lc-J/Grid2⁺
• Genetic Background: involves: 129X1/SvJ * BALB/cByJ * C57BL/6

behavior/neurological

ataxia ( J:62117 )

• a swaying ataxia is found in the third week of age, the same as in simple lurcher heterozygotes

nervous system

nervous system phenotype ( J:62117 )

N • disruption of Bax rescues the granule cell death normally found in Lurcher mice such that these mice have a nearly normal, large cell-dense inner granule cell layer and normal lobular pattern of the cerebellar cortex

abnormal cerebellar Purkinje cell layer ( J:62117 )

abnormal Purkinje cell morphology ( J:62117 )

• at 30 days of age immunohistochemistry shows that the Purkinje cells are not aligned in a monolayer and have stunted, poorly developed dendritic trees that fail to reach the pial surface, similar to the morphology found in Bax wild-type lurcher heterozygotes

abnormal Purkinje cell dendrite morphology ( J:62117 )

decreased Purkinje cell number ( J:62117 )

• there are few Purkinje cells at the interface of the inner granule cell layer and molecular layer, and, although cell counts show that there are 15% of normal numbers at 30 days of age, which is significantly more than the 6% normal level found in Bax wild-type lurcher heterozygotes, by 300 days of age the double mutant mice have only 1% of normal Purkinje cell numbers

abnormal cerebellar granule layer morphology ( J:62117 )

• although there are fewer than normal granule cells per midsagittal cerebellar section, there are approximately 60% of normal numbers which is a significant increase over the Bax wild-type lurcher heterozygotes

Genotype
MGI:4360655

cx11

• Allelic Composition: Bax^tm1Sjk/Bax⁺; Grid2^Lc-J/Grid2⁺
• Genetic Background: involves: 129X1/SvJ * BALB/cByJ * C57BL/6

behavior/neurological

ataxia ( J:62117 )

• a swaying ataxia is found in the third week of age, the same as in simple lurcher heterozygotes

nervous system

reduced cerebellar foliation ( J:62117 )

abnormal cerebellar Purkinje cell layer ( J:62117 )

• gaps in the Purkinje cell layer found by 15 days of age

decreased Purkinje cell number ( J:62117 )

abnormal cerebellar granule layer morphology ( J:62117 )

• much smaller internal granule cell layer as early as 15 days of age

decreased cerebellar granule cell number ( J:62117 )