Phenotypes Associated with This Genotype

Genotype
MGI:2682556

• Allelic Composition: Slc6a5^tm1Betz/Slc6a5^tm1Betz
• Genetic Background: involves: 129P2/OlaHsd

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

mortality/aging

postnatal lethality, complete penetrance ( J:86625 )

• homozygotes die around the end of the second week after birth, exhibiting a complex neuromotor phenotype

• death is probably due to an inability to feed, desiccation, and continued convulsions

growth/size/body

slow postnatal weight gain ( J:86625 )

• homozygotes display normal birth weights but gain weight more slowly than wild-type littermates postnatally

behavior/neurological

impaired righting response ( J:86625 )

• at P10, most homozygotes display a severely impaired righting response

• when turned on their backs, homozygotes consistently fail to turn themselves and regain the upright position

hyperekplexia ( J:86625 )

• after 1 week of life, homozygotes exhibit a lethal neuromotor disorder characterized by muscular spasticity, tremor, and an inability to right

limb grasping ( J:86625 )

• when lifted by the tail, homozygotes clasp their hindfeet between episodes of tremor, whereas wild-type and heterozygous control mice tend to move heavily while spreading out their legs

tremors ( J:86625 )

• at P10, all homozygotes develop strong spontaneous tremors, as revealed by the high amplitudes of electromechanical tracings of tremor-derived movement recordings

• only a very low number of homozygotes show spasticity and tremors at P9

muscle

muscle hypertonia ( J:86625 )

• at P10, most homozygotes exhibit spasticity and a rigid muscle tone

• usually, signs of increased muscle tone are already evident at P8

• however, no histological changes are detected in skeletal muscle at P10

nervous system

nervous system phenotype ( J:86625 )

N • at P10, homozygotes display normal brain stem and spinal cord histology relative to wild-type mice

N • despite low glycine transport activity in caudal regions of the CNS, homozygotes show no compensatory changes in the expression and synaptic localization of glycine transport-related synaptic proteins

abnormal CNS synaptic transmission ( J:86625 )

• homozygotes exhibit impaired transport of extracellular glucine into presynaptic boutons

abnormal inhibitory postsynaptic currents ( J:86625 )

• homozygotes display a significant reduction in the mean amplitude and frequency of glycinergic IPSCs recorded from hypoglossal motoneurons in situ at P8 and P9

abnormal miniature inhibitory postsynaptic currents ( J:86625 )

• in the presence of 0.5 uM tetrodotoxin and 100 mM sucrose, homozygotes display a significant reduction in the mean amplitude and frequency of glycinergic mIPSCs recorded from hypoglossal motoneurons in situ at P8 and P9; however, the kinetics of mIPSC decay remain relatively unchanged

• in the presence of 0.5 uM tetrodotoxin, homozygotes show a ~42% reduction in the peak amplitude of the average glycinergic mIPSC recorded from cultured spinal neurons after 21 days of vitro differentiation; however, the burst frequency and decay kinetics of glycinergic mIPSCs remain relatively unchanged

decreased miniature inhibitory postsynaptic current amplitude ( J:86625 )

• in the presence of 0.5 uM tetrodotoxin and 100 mM sucrose, homozygotes display a significant reduction in the mean amplitude of glycinergic mIPSCs recorded from hypoglossal motoneurons in situ at P8 and P9

• in the presence of 0.5 uM tetrodotoxin, homozygotes show a ~42% reduction in the peak amplitude of the average glycinergic mIPSC recorded from cultured spinal neurons after 21 days of vitro differentiation

decreased miniature inhibitory postsynaptic current frequency ( J:86625 )

• in the presence of 0.5 uM tetrodotoxin and 100 mM sucrose, homozygotes display a significant reduction in the mean frequency of glycinergic mIPSCs recorded from hypoglossal motoneurons in situ at P8 and P9

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
hyperekplexia 3		DOID:0060698	OMIM:614618	J:86625