Mouse Genome Informatics
hm
    Slc6a5tm1Betz/Slc6a5tm1Betz
involves: 129P2/OlaHsd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
mortality/aging
• 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
• homozygotes display normal birth weights but gain weight more slowly than wild-type littermates postnatally

behavior/neurological
• 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
• after 1 week of life, homozygotes exhibit a lethal neuromotor disorder characterized by muscular spasticity, tremor, and an inability to right
• 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
• 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
• 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
N
• at P10, homozygotes display normal brain stem and spinal cord histology relative to wild-type mice (J:86625)
• 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 (J:86625)
• homozygotes exhibit impaired transport of extracellular glucine into presynaptic boutons
• homozygotes display a significant reduction in the mean amplitude and frequency of glycinergic IPSCs recorded from hypoglossal motoneurons in situ at P8 and P9
• 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

Mouse Models of Human Disease
OMIM IDRef(s)
Hyperekplexia 3; HKPX3 614618 J:86625