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Phenotypes Associated with This Genotype
Genotype
MGI:3715869
Allelic
Composition
Slc25a12Gt(OST123999)Lex/Slc25a12Gt(OST123999)Lex
Genetic
Background
involves: 129S5/SvEvBrd * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Slc25a12Gt(OST123999)Lex mutation (0 available); any Slc25a12 mutation (102 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• many die between E18 and P15 with almost none surviving beyond 22 days (J:101164)

homeostasis/metabolism
• striatal GABA is reduced to 60% of wild-type levels
• taurine levels are increased in the brain
• striatum shows a reduction in dopamine (to 64%) and its metabolites, 3-MT (to 43%) and HVA (to 68%)
• however, DOPAC content in the striatum is normal, resulting in increased DOPAC/dopamine ratio
• the limbic system shows a reduction in dopamine (57%) and DOPAC (50%), but only a nonsignificant decrease in HVA
• these results suggest impaired dopamine release and increased intraneuronal metabolism of dopamine in the striatum
• decrease in 5-HT levels and its intracellular degradation product 5-HIAA in diencephalon and brainstem

nervous system
• N-acetylaspartate brain content is at 36 and 29% of wild type values at P10 and P20, respectively (J:101164)
• N-acetylaspartylglutamate brain levels remain at about 60 and 80% of wild type at P10 and P20, respectively (J:101164)
• aspartate concentration in the brain is about 11 and 6% of wild type at P10 and P20, respectively (J:101164)
• decrease in whole brain glutamine content which is more prominent in the straitum (29% of wild-type levels) (J:193095)
• however, brain aspartate, serine and alanine levels are normal and noradrenaline content is normal (J:193095)
• P17 mice show a decrease in N-acetylaspartate levels in the brain, with decreases seen in the cortex gray matter, the frontal white matter, and brainstem regions (J:243212)
• taurine levels are increased in the brain (J:243212)
• however, lactate levels in the brain of P17 mice are similar to wild-type mice (J:243212)
• reduction in size of the striatum, with the striatum/brain ratio size reduced to 80%
• marker analysis indicates a deficiency in maturation of medium spiny GABA neurons in the striatum
• monoamine metabolism is impaired in the brain, with increased intraneuronal metabolism of dopamine in the striatum but not the limbic system
• develop by day 19 to 21
• striatal GABA is reduced to 60% of wild-type levels
• decrease in 5-HT levels and its intracellular degradation product 5-HIAA in diencephalon and brainstem
• at day 18 to 20, hypomyelination occurs in the central nervous system, such as in the corpus callosum, white matter of the cerebral cortex, anterior commissure, internal capsule, and pyramidal tract
• myelin-specific protein levels are decreased at 20 days
• the increased DOPAC/dopamine ratio suggest impaired dopamine release

behavior/neurological
• in the aversive (lighted) condition of the open field, mice travel less distance in periphery, indicating increased anxiety
• mice exhibit increased thigmotaxic behavior in darkness in the open field, indicating increased anxiety
• mice show a limb clasping phenotype instead of a normal escape posture
• occur after day 16
• on the balance beam, mice tend to lock in a fixed spastic posture while on the beam and almost all fall off the bar
• after day 14 mice display impaired coordination in a hanging wire test
• mice show a lack of motor coordination in the hindlimbs
• develop by day 19 to 21
• vertical activity tends to be higher in the darkness condition
• total distance traveled in darkness in the open field is increased
• mice are as fast as wild-type mice but have a lower resting time, indicating hyperactivity
• in the aversive (lighted) condition of the open field, mice show a burst of speed in the center of the arena, indicating hyperactivity
• mice exhibit a shorter stride length and hindpaw base width and an erratic direction of path and incoordination
• mice exhibit hyper-reactivity in the toe pinch test and an exacerbated response to a finger stroke in the touch escape test
• however, no alternations in other sensory function in visual placing, blast response, tactile and vibrissae orientation, are seen
• develop by day 19 to 21

growth/size/body
• when mice die they are 22% of the weight of a wild-type mouse
• weights of several organs (including liver, kidney, heart, brain, thymus, lung, spleen, stomach, and bone and skeletal muscle) are decreased

cellular
• cell respiration is deceased in neurons but not in astrocytes
• however, neurons and astrocytes show normal glucose consumption and lactate production
• respiration rate with glutamate plus malate in skeletal muscle is reduced to about 50% of that in wild type, but observe no differences when using pyruvate and malate
• malate-aspartate shuttle (MAS) activity in skeletal muscle and brain mitochondria is very low
• aspertate formation from glutamate and malate by isolated brain mitochondria is reduced
• increase in oxidative stress in the striatum as shown by a decreased GSH/GSSG ratio

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
early infantile epileptic encephalopathy 39 DOID:0080349 OMIM:612949
J:243212


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
08/13/2019
MGI 6.14
The Jackson Laboratory