All Phenotypes Kcnj10<tm1Lst> MGI Mouse

Mouse Models of Human Disease	DO ID	OMIM ID(s)	Ref(s)
EAST syndrome	DOID:0060484	OMIM:612780	J:226598

postnatal lethality, complete penetrance ( J:63635 , J:77663 , J:108878 )

• after P7, homozygotes show a higher rate of mortality; however, most mutants survive up to 3 weeks of age, permitting examination of retinal physiology after eyelid opening (P13 and P14) (J:63635)

• the first deaths occur at P8, with 100% mortality at P24 (J:77663)

• most deaths occur at P9-P21 (J:108878)

abnormal motor capabilities/coordination/movement ( J:77663 )

• by P10-P12, homozygotes exhibit defects in controlling voluntary movements, posture, and balance; these defects increase in severity over time

absent pinna reflex ( J:75599 )

• homozygotes show absence of a Preyer reflex

absent startle reflex ( J:108878 )

• at P12-P18, homozygotes fail to display an auditory startle response at the highest test stimulus (120 dB)

• in contrast, homozygotes startle appropriately to tactile stimuli (e.g. air puffs)

• no circling, head tilting or other signs of the classical shaker/salzer phenotype are observed

tremors ( J:77663 )

• by the third postnatal week, homozygotes display a body tremor

abnormal motor coordination/balance ( J:63635 , J:77663 )

• homozygotes exhibit motor coordination deficits, first apparent at ~2 weeks of age (J:63635)

• in contrast to wild-type littermates, homozygotes are unable to climb a grid at an 80 angle and fall off (J:77663)

impaired righting response ( J:108878 )

• at P8-P10, homozygotes develop a severe motor impairment with difficulties righting themselves

impaired balance ( J:63635 )

• by P10-P12, homozygotes exhibit loss of balance and occasionally fall on their side

jerky movement ( J:63635 )

• by P10-P12, homozygotes show awkward and jerky movements

weakness ( J:77663 )

• by P8-P10, homozygotes display progressive weakness

abnormal posture ( J:77663 )

• by P10-P12, homozygotes exhibit defects in posture, with frequent falls and rollovers and reduced ability to regain the upright position

hindlimb paralysis ( J:77663 )

• homozygotes drag their hindlimbs, indicating paralysis

decreased body size ( J:63635 , J:77663 )

• after P7, homozygotes are considerably smaller than wild-type littermates (J:63635)

• by P10-P12, homozygotes are readily identifiable by their smaller size (J:77663)

decreased body weight ( J:77663 )

• by P10-P12, homozygotes are readily identifiable by their decreased body weight

postnatal growth retardation ( J:63635 , J:77663 , J:108878 )

• homozygotes stop gaining body weight by P8-P10 (J:77663)

hearing/vestibular/ear phenotype ( J:75599 )

N

• at P17-P21, the thickness of stria vascularis in the first cochlear turn appears normal, indicating that absence of EP is not due merely to degeneration of intermediate cells

• the tunnel of Corti appears fully developed at the time of electrophysiological measurements (P17-P21)

• at P17-P21, the endolymphatic [K+] in the utricle is not different from that of wild-type mice

• at P17-21, no collapse of the vestibular labyrinth is noted, and the major cells types of the ampulla (hair cells, transitional cells, and dark cells) appear normal

• at P17-P21, the utricular potential (UP) is similar to that observed in wild-type mice

abnormal cochlea morphology ( J:108878 )

• from P6 to P18, homozygotes display pathological changes at the apical, medial and basal cochlea

• at P6, only subtle changes are observed, while the organ of Corti remains morphologically normal

abnormal Reissner membrane morphology ( J:75599 , J:108878 )

• at P17-P21, a large displacement of the Reissner's membrane is observed in the first cochlear turn (J:75599)

• at P6, both epithelial layers of Reissner membrane show degenerative changes, with numerous necrotic cells in both the endolymphatic cuboidal epithelium lining the cochlear duct and in the perilymphatic squamous epithelium (J:108878)

• at P9, Reissner membrane becomes progressively atrophic (J:108878)

collapsed Reissner membrane ( J:108878 )

• by P18, Reissner's membrane is collapsed and nearly aligned onto the stria vascularis

distended Reissner membrane ( J:108878 )

• at P6, Reissner membrane appears distended while other structures of the cochlear duct appear normal

abnormal scala media morphology ( J:108878 )

• homozygotes show progressive collapse of the scala media compartment

cochlear inner hair cell degeneration ( J:108878 )

• at P9, IHCs display signs of degeneration (i.e atrophy, vacuolated cytoplasm); however, no obvious changes are noted at P6

• by P18, IHCs are completely absent

cochlear outer hair cell degeneration ( J:108878 )

• at P9, OHCs display signs of degeneration (i.e atrophy, vacuolated cytoplasm); however, no obvious changes are noted at P6

• by P18, OHCs are completely absent

organ of Corti degeneration ( J:108878 )

abnormal stria vascularis morphology ( J:108878 )

• at P9 and P18, the stria vascularis is significantly atrophic

abnormal tectorial membrane morphology ( J:108878 )

• at P9, the tectorial membrane is swollen and shows disorganization in the direction of fibers

• by P18, the tectorial membrane is markedly swollen and atrophic with an irregular direction of fibers, undulating and crisscrossing

vestibular hair cell degeneration ( J:108878 )

• at P9, mainly type I hair cells exhibit apoptotic nuclei

• in contrast, type II cells and supporting cells appear normal

abnormal crista ampullaris neuroepithelium morphology ( J:108878 )

utricular macular degeneration ( J:108878 )

vestibular saccular macula degeneration ( J:108878 )

• at P9, the saccular membrane is collapsed

abnormal cochlear endolymph ionic homeostasis ( J:75599 )

• at P17-P21, the cochlear endolymphatic [K+] is greatly reduced and the endolymphatic space is partially collapsed

absent endocochlear potential ( J:75599 )

• at P17-P21, the endocochlear potential (EP) is abolished

increased or absent threshold for auditory brainstem response ( J:75599 )

• at P17-P21, homozygotes exhibit an auditory brain stem response threshold >81 dB

impaired hearing ( J:75599 )

• at P17-P21, hearing is severely compromised as shown by the absence of a Preyer reflex

vision/eye phenotype ( J:63635 )

N	• at P11 and P18-P21, mutant retinas show normal organization with no obvious lamination defects

abnormal eye electrophysiology ( J:63635 )

• in situ measurements of the input resistance of mutant Muller cells indicate an ~10-fold higher resistance relative to wild-type cells

• the resting membrane potential is significantly depolarized, indicating that Muller cell K+ conductance is significantly reduced

• the slow PIII response of the light-evoked electroretinogram, present in wild-type retinas, is completely absent; this response is also absent in wild-type preparations treated with Ba2+ to block Muller cell K+ channels

• in contrast, the b-wave of the ERG is not eliminated, indicating that the b-wave is not generated by K+ currents flowing through Muller cells

cochlear inner hair cell degeneration ( J:108878 )

• by P18, IHCs are completely absent

• at P9, IHCs display signs of degeneration (i.e atrophy, vacuolated cytoplasm); however, no obvious changes are noted at P6

cochlear outer hair cell degeneration ( J:108878 )

• at P9, OHCs display signs of degeneration (i.e atrophy, vacuolated cytoplasm); however, no obvious changes are noted at P6

• by P18, OHCs are completely absent

vestibular hair cell degeneration ( J:108878 )

• at P9, mainly type I hair cells exhibit apoptotic nuclei

• in contrast, type II cells and supporting cells appear normal

abnormal oligodendrocyte morphology ( J:77663 )

• in vitro, mutant oligodendrocytes do not elaborate membrane sheaths, display a large somatic area and fewer branches, and rarely interact with other cells, indicating morphological immaturity

• in contrast, spinal cord neurons from P0-P12 homozygotes exhibit normal physiological and morphological characteristics

cochlear ganglion degeneration ( J:108878 )

• at P18, homozygotes show a ~50% loss of spiral ganglia neurons and fibers and surrounding non-neuronal cells

• however, the cytoplasm spiral ganglia neurons and their peripheral processes appear normal at P6 and P9

vestibular ganglion degeneration ( J:108878 )

• at P9, homozygotes display significant degeneration of vestibular ganglia; some neurons have apoptotic nuclei and neuronal cell bodies are missing in certain areas

abnormal cochlear nerve morphology ( J:108878 )

• at P9, the cochlear (VIIIth) nerve bundle is markedly atrophic

• central processes of spiral ganglion neurons degenerate, with severe degeneration in the VIIIth nerve which contains their axons

abnormal spinal cord morphology ( J:77663 )

• at P9, TUNEL staining in spinal cord indicates specific labeling of small nuclei in the gray matter and in distal areas of the white matter, indicating apoptosis of glial cells

abnormal spinal cord white matter morphology ( J:77663 )

• homozygotes display numerous round and oval vacuoles of varying sizes in the white matter of the spinal cord

• smaller vacuoles contain membranous elements of unknown origin and abnormal myelin sheaths

• in some cases, dysmyelination is accompanied by axonal degeneration

axon degeneration ( J:77663 )

• in some cases, hypomyelination or dysmyelination of the spinal cord is accompanied by axonal swellings and degeneration

abnormal myelination ( J:77663 )

• at P9, homozygotes exhibit hypomyelination and massive spongiform vacuolation in spinal cord, primarily affecting the white matter and neuropil with severe axonal pathology

• by P18, vacuolation has progressed in inner areas of the white matter

• other defects, including shrunken motoneuron cell bodies, are observed in some gray matter areas

• at P12, magnetic resonance images show hyperintense lesions throughout the whole spinal cord including brainstem areas; however, the cerebellum, midbrain, and cortical regions appear unaffected

abnormal nervous system electrophysiology ( J:77663 )

• in vitro, cultured oligodendrocytes from the developing spinal cord show complete absence of inwardly rectifying K+ currents and a depolarized membrane potential

dehydration ( J:77663 )

• by P10-P12, homozygotes are readily identifiable by their dehydrated appearance

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

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

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

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