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Phenotypes Associated with This Genotype
Genotype
MGI:2682534
Allelic
Composition
Slc6a9tm1Betz/Slc6a9tm1Betz
Genetic
Background
involves: 129P2/OlaHsd * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Slc6a9tm1Betz mutation (0 available); any Slc6a9 mutation (24 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• newborn homozygotes are externally normal but gradually fail to thrive and die within 6-14 hrs after birth most likely due to respiratory failure combined with an inability to suckle

behavior/neurological
• newborn homozygotes lack milk in their stomachs
• newborn homozygotes are unable to suckle
• newborn homozygotes are hyporesponsive to mild tactile stimuli such as gentle touch
• when picked up and nipped by their tail, newborn homozygotes display only a weak (8/10) or no (2/10) tail pinching response
• upon mild tactile stimulation, newborn homozygotes assume an abnormal body posture with dropping forelimbs
• newborn homozygotes display only weak or no spontaneous motor activity

respiratory system
• newborn homozygotes display a severe breathing irregularity
• however, no histologic abnormalities of the airways or lungs are observed and the musculo-skeletal system appears unaffected
• newborn homozygotes show a severe depression of respiratory frequencies to only 16% of those in wild-type pups, as shown by whole-body plethysmography
• although durations of single breaths are only marginally longer, expiratory intervals are significantly prolonged as shown by a 4-fold increase of the coefficient of variation relative to that in control littermates
• newborn homozygotes exhibit long periods of apnea interrupted by gasp-like inspirations
• newborn homozygotes exhibit long periods of apnea interrupted by gasp-like inspirations

growth/size/body
• newborn homozygotes weigh ~15% less than control littermates

homeostasis/metabolism

muscle

nervous system
N
• newborn homozygotes display normal brain stem and spinal cord histology
• no major adaptive changes in synapse biochemistry or differences in synaptic protein expression are observed in the CNS
• the density and morphology of glial cells appear unaffected
• P2 membrane fractions from newborn homozygotes show a >70% and >80% reduction of [3H]glycine uptake in frontal brain and CNS caudal regions, respectively, relative to wild-type controls
• increased accumulation of extracellular glycine leads to a sustained activation of inhibitory glycine receptors and results in suppression of the respiratory network activity
• in vitro analysis of inspiratory activity in mutant brain stem slices indicates prolonged periods of inactivity and a significantly reduced burst frequency with variable interburst intervals relative to the regular rhythmic bursting observed in control slices
• application of the glycine receptor antagonist strychnine (2 uM) increases burst activity by 3.6-fold leading to a frequency comparable to that seen under control conditions in wild-type mice; however, the activity of mutant slices is consistently more irregular than that of wild-type preparations
• the coefficient of variation of the interburst interval is significantly higher in mutant slices and is only partially improved upon strychnine application
• however, no differences in rise time and burst duration are observed between brain stem slices from wild-type and mutant mice
• application of the GABAA receptor antagonist bicuculline (1-2 uM) fails to normalize the rhythmic burst patterns observed in mutant slices
• application of the NMDA receptor blockers MK-801 (10 uM) and AP-5 (100 uM) fails to restore a regular respiratory rhythm in mutant slices
• whole-cell recordings from hypoglossal motoneurons at a holding potential of -70 mV indicate that during periods without obvious IPSCs, the average noise values recorded from mutant neurons are significantly higher than those observed in wild-type cells
• the average interval of IPSCs identified in mutant hypoglossal motoneurons is significantly lower than in wild-type cells, whereas the average IPSC amplitude is not significantly smaller than that in wild-type cells
• the IPSC decay time is significantly longer in mutant neurons relative to wild-type cells
• application of strychnine decreases the steady-state holding current in mutant hypoglossal motoneurons and reduces synaptic noise to wild-type levels

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
glycine encephalopathy DOID:9268 OMIM:605899
J:86624


Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO)
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last database update
03/12/2024
MGI 6.23
The Jackson Laboratory