Phenotypes associated with this allele

• Allele Symbol: Slc1a3^tm1Kta
• Allele Name: targeted mutation 1, Kohichi Tanaka
• Allele ID: MGI:1931872
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Slc1a3^tm1Kta/Slc1a3^tm1Kta	B6.129P2-Slc1a3^tm1Kta	MGI:4417921
hm2	Slc1a3^tm1Kta/Slc1a3^tm1Kta	involves: 129P2/OlaHsd	MGI:3033217

Genotype
MGI:4417921

hm1

• Allelic Composition: Slc1a3^tm1Kta/Slc1a3^tm1Kta
• Genetic Background: B6.129P2-Slc1a3^tm1Kta

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

vision/eye

vision/eye phenotype ( J:124191 )

N • despite retinal ganglion cell loss and glaucomatous-like changes, mice exhibit normal intraocular pressure

abnormal optic nerve morphology ( J:124191 )

• at 8 months, the optic nerve is thinner than in wild-type mice

optic nerve cupping ( J:124191 )

• at 8 months

optic nerve degeneration ( J:124191 )

• mice exhibit optic nerve degeneration with reduction of optic nerve area, degeneration of axons, and reduced axon density compared to in wild-type mice

abnormal retina ganglion layer morphology ( J:124191 )

• fewer cells are found in the retinal ganglion layer and consist of displaced amacrine cells compared to in wild-type mice

decreased retina ganglion cell number ( J:124191 )

• after 2 weeks, mice exhibit loss of retinal ganglion cells (RGCs) associated with oxidative stress unlike wild-type mice

• retinal ganglion cell loss is increased when retinal ganglion cells are mixed with Muller cells treated with hydrogen peroxide unlike cells mixed with similarly treated wild-type Muller cells

• however, treatment with menantine prevents RGC loss

abnormal retina inner nuclear layer morphology ( J:124191 )

• fewer cells are found in the retinal inner nuclear layer compared to in wild-type mice

retina degeneration ( J:124191 )

• after 8 weeks, mice exhibit loss of retinal ganglion cells (RGCs) unlike wild-type mice

abnormal electroretinogram waveform feature ( J:124191 )

• mice exhibit impaired multifocal electroretinogram compared with wild-type mice

cellular

increased cellular sensitivity to hydrogen peroxide ( J:124191 )

• retinal ganglion cell loss is increased when retinal ganglion cells are mixed with Muller cells treated with hydrogen peroxide unlike cells mixed with similarly treated wild-type Muller cells

homeostasis/metabolism

increased lactate dehydrogenase level ( J:124191 )

• in retinal ganglion cells cultured with hydrogen peroxide treated Muller cells

nervous system

decreased retina ganglion cell number ( J:124191 )

• after 2 weeks, mice exhibit loss of retinal ganglion cells (RGCs) associated with oxidative stress unlike wild-type mice

• retinal ganglion cell loss is increased when retinal ganglion cells are mixed with Muller cells treated with hydrogen peroxide unlike cells mixed with similarly treated wild-type Muller cells

• however, treatment with menantine prevents RGC loss

abnormal optic nerve morphology ( J:124191 )

• at 8 months, the optic nerve is thinner than in wild-type mice

optic nerve cupping ( J:124191 )

• at 8 months

optic nerve degeneration ( J:124191 )

• mice exhibit optic nerve degeneration with reduction of optic nerve area, degeneration of axons, and reduced axon density compared to in wild-type mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
low tension glaucoma		DOID:13544		J:124191

Genotype
MGI:3033217

hm2

• Allelic Composition: Slc1a3^tm1Kta/Slc1a3^tm1Kta
• Genetic Background: involves: 129P2/OlaHsd

behavior/neurological

behavior/neurological phenotype ( J:46746 )

N • no ataxic gait or intention tremors

N • spontaneous activity in a new environment is also normal

abnormal motor coordination/balance ( J:46746 )

• although ability to maintain balance on a slowly rotating rotorod was normal, ability to maintain balance at higher speeds (20RPM) was impaired

seizures ( J:58180 )

increased susceptibility to pharmacologically induced seizures ( J:58180 )

• seizures induced by pentylenetetrazole (PTZ) are more severe and prolonged

abnormal kindling response ( J:58180 )

• initial seizure development and duration after kindling were normal but duration of stage 3 seizures was significantly prolonged

hearing/vestibular/ear

cochlear inner hair cell degeneration ( J:99715 )

• at 7 days after kanamycin treatment, homozygotes exhibit a significantly higher rate of IHC degeneration in the middle region of the cochlea relative to similarly-treated wild-type mice

• in contrast, both kanamycin-treated mutant and wild-type mice display >90% of OHC degeneration

abnormal auditory brainstem response waveform shape ( J:66146 )

• prior to noise-exposure, homozygotes exhibit a reduction in amplitudes of all five principal waves but no detectable change in latencies

increased or absent threshold for auditory brainstem response ( J:66146 )

• prior to noise-exposure, homozygotes exhibit slightly but significantly higher ABR thresholds (~10 dB) relative to wild-type

• however, no excitotoxic damage (i.e. afferent dendrite swelling below IHCs) is noted at pre-sound exposure

increased susceptibility to noise-induced hearing loss ( J:66146 )

• homozygotes show a significant increase in noise-induced hearing loss due to increased accumulation of glutamate in perilymphs

• after noise-exposure (4 kHz pure tone at a 105 dB SPL for 30 min), homozygotes show a significant rise in ABR thresholds and a significant delay in the recovery of ABR thresholds relative to wild-type mice

• at 2 hrs after noise-exposure, homozygotes continue to display massive afferent dendrite swelling below IHCs, whereas wild-type IHC and dendrites return to normal morphology

increased susceptibility to ototoxicity-induced hearing loss ( J:99715 )

• at 7 days after kanamycin treatment, homozygotes show a significantly greater shift in ABR thresholds at click sound and 8 kHz, but not at 4 and 1 kHz, relative to wild-type mice

• however, untreated homozygotes display no significant differences in average ABR thresholds relative to wild-type mice

nervous system

nervous system phenotype ( J:46746 )

N • cerebellar anatomy and development were normal

cochlear inner hair cell degeneration ( J:99715 )

• at 7 days after kanamycin treatment, homozygotes exhibit a significantly higher rate of IHC degeneration in the middle region of the cochlea relative to similarly-treated wild-type mice

• in contrast, both kanamycin-treated mutant and wild-type mice display >90% of OHC degeneration

abnormal Purkinje cell morphology ( J:46746 )

• more multiple innervation of purkinje cells by climbing fibers in adults than normal

abnormal nervous system physiology ( J:46746 )

• edemas resulting from cold injury are much larger than normal in the cerebellum but are of normal size in the cerebrum

seizures ( J:58180 )

increased susceptibility to pharmacologically induced seizures ( J:58180 )

• seizures induced by pentylenetetrazole (PTZ) are more severe and prolonged

abnormal kindling response ( J:58180 )

• initial seizure development and duration after kindling were normal but duration of stage 3 seizures was significantly prolonged

abnormal synaptic glutamate release ( J:66146 )

• prior to noise-exposure, homozygotes exhibit a significant increase in the basal glutamate level in the perilymph relative to wild-type mice

• during and after 105 dB sound exposure, homozygotes show a significant rise in glutamate concentration in the perilymph, whereas no significant increase is noted in wild-type mice

homeostasis/metabolism

increased susceptibility to ototoxicity-induced hearing loss ( J:99715 )

• at 7 days after kanamycin treatment, homozygotes show a significantly greater shift in ABR thresholds at click sound and 8 kHz, but not at 4 and 1 kHz, relative to wild-type mice

• however, untreated homozygotes display no significant differences in average ABR thresholds relative to wild-type mice