Phenotypes associated with this allele

• Allele Symbol: Grm6^em#Mrho
• Allele Name: endonuclease-mediated mutation, Mrinalini Hoon
• Allele ID: MGI:8272179
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Grm6^em#Mrho/Grm6^em#Mrho	C57BL/6J-Grm6^em#Mrho	MGI:8272181
ht2	Grm6^em#Mrho/Grm6^+	C57BL/6J-Grm6^em#Mrho	MGI:8272182

Genotype
MGI:8272181

hm1

• Allelic Composition: Grm6^em#Mrho/Grm6^em#Mrho
• Genetic Background: C57BL/6J-Grm6^em#Mrho

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

vision/eye

decreased b-wave amplitude ( J:371980 )

• rod-dominated (scotopic) electroretinograms (ERGs) show no appreciable b-wave

abnormal eye electrophysiology ( J:371980 )

• retinal ganglion cells (RGCs) display no light-evoked responses, indicating complete ON retinal pathway suppression

• voltage-clamp recordings show absent light-driven excitation and inhibition in ON sustained alpha (ONalpha) RGCs

• current-clamp recordings to measure the resting membrane potential of ONalpha RGCs show that RGCs are hyperpolarized relative to wild-type or heterozygous RGCs

• ONalpha RGCs exhibit reduced spiking ability in response to depolarizing current injections

• OFF-sustained (OFF-sus) alpha RGCs fail to suppress spiking during dim light flashes applied from darkness and show a reduced peak spike rate at light offset, with RGCs showing mild improvement at moderate light conditions and normal spike suppression under bright conditions, indicating that OFF-sus RGCs show the most severe impairments in their ability to fire properly at dim-light levels

• OFF-sus alpha RGCs are almost insensitive to contrast at both moderate and bright light luminance levels and thus incapable of contrast encoding, with reduced slope of the contrast response curve

• in summary, lack of ON pathway input disrupts the contrast sensitivity of OFF-sus RGCs

abnormal retinal bipolar cell electrophysiology ( J:371980 )

• dendrites of rod bipolar cells show no response to a light flash

decreased visual acuity ( J:371980 )

• in the optomotor response assay, mice exhibit reduced visual acuity

abnormal visual contrast sensitivity ( J:371980 )

• in the optomotor response assay, mice exhibit reduced contrast sensitivity

nyctalopia ( J:371980 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
congenital stationary night blindness 1B		DOID:0110865	OMIM:257270	J:371980

Genotype
MGI:8272182

ht2

• Allelic Composition: Grm6^em#Mrho/Grm6⁺
• Genetic Background: C57BL/6J-Grm6^em#Mrho

nervous system

abnormal excitatory synapse morphology ( J:371980 )

• ONalphas have an upregulation excitatory synaptic proteins

• however, excitatory snapse number, volume, and shape are normal

increased excitatory postsynaptic current amplitude ( J:371980 )

• ON sustained alpha (ONalpha) retinal ganglion cells (RGCs) generate spontaneous excitatory postsynaptic currents (sEPSCs) with elevated peak amplitudes compared to wild-type, without differences in sEPSC kinetics or event frequency, indicating that ONalphas upregulate the strength of excitatory synapses to preserve output

vision/eye

abnormal eye electrophysiology ( J:371980 )

• OFF-sustained (OFF-sus) alpha RGCs show abnormally elevated baseline spiking in response to dim light flash applied from darkness and both spike suppression duration and peak spike rate following light onset are reduced, with RGCs showing nearly normal spiking and duration of spike suppression under moderate light conditions and suppress spikes normally under bright conditions, indicating that OFF-sus RGCs show the most severe impairments in their ability to fire properly at dim-light levels

• OFF-sus RGCs shown a normal contrast response curve at moderate-light level and reduced slope at bright-light level, however in the optomotor response assay, mice exhibit normal visual acuity and contrast sensitivity

• inhibitory input to OFF-sus RGCs is reduced at bright-light level; at this bright-light level, the reduced inhibitory conductance has minimal impact on spike output in response to static stimuli

abnormal retinal bipolar cell electrophysiology ( J:371980 )

• dendrites of rod bipolar cells show an approximate 50% attenuated responses to a light flash

• however, excitatory and inhibitory inputs as well as spike outputs remain comparable to wild-type, indicating compensation that preserves ON pathway function

• rod bipolar cells show normal resting membrane potential in current-clamp recordings and input resistance and capacitance remain unaltered for ONalpha RGCs