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Phenotypes Associated with This Genotype
Genotype
MGI:5829465
Allelic
Composition
Slc7a5tm1.1Daca/Slc7a5tm1.1Daca
Tg(Tek-cre)12Flv/0
Genetic
Background
B6J.Cg-Slc7a5tm1.1Daca Tg(Tek-cre)12Flv
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Slc7a5tm1.1Daca mutation (1 available); any Slc7a5 mutation (31 available)
Tg(Tek-cre)12Flv mutation (1 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
homeostasis/metabolism
• polysome profiling of brain cortical lysates showed a significant shift of ribosomes from actively translating polysomes toward the monosomal fraction, indicating decreased mRNA translation initiation in the brain
• after birth (P2-P14) and in adult stages (>P40), brain levels of branched-chain amino acids (BCAAs), esp. leucine and isoleucine, are abnormally low while levels of a few other amino acids (e.g., histidine, serine, and phenylalanine) are increased relative to those in age-matched controls
• brain histidine levels are several fold higher than in control mice
• brain levels of leucine and isoleucine are normalized after 3 weeks of intracerebroventricular (i.c.v.) BCAA (leucine and isoleucine) delivery
• brain levels of several other large neutral amino acids (LNAAs) including tyrosine and tryptophan are relatively normal, and serum amino acid levels are unchanged
• no major changes in brain LNAA and BCAA levels are noted at E14.5
• brain levels of phenylalanine are increased
• brain serine levels are modestly but significantly increased
• mice show abnormal activation of the amino acid response (AAR) signal transduction pathway in the brain

behavior/neurological
• at P55-P65, mice exhibit motor delay and autism-like phenotypes
• some neurobehavioral phenotypes can be rescued by i.c.v. administration of leucine and isoleucine in adulthood
• mice do not show excessive grooming or stereotyped behavior in the marble burying test
• 89% of mice display hind limb clasping
• fewer mice (50%) show clasping after 3 weeks of i.c.v. BCAA delivery
• mice show increased latency to cross the beam in the walking beam test
• in the footprint test, mice show decreased stride and stance length and increased sway length relative to controls
• gait is improved after 3 weeks of i.c.v. BCAA delivery with complete normalization of the sway length
• rearing is significantly reduced
• number of rearings is normalized after 3 weeks of i.c.v. BCAA delivery
• mice show reduced explorative behavior and lower velocity in an open field test
• open field activity is normalized after 3 weeks of i.c.v. BCAA delivery
• in the three chamber sociability test, P55-P65 mice fail to show preference for an unfamiliar caged wild-type mouse over a caged object, unlike controls
• in the juvenile social interaction test, P25-P35 mice tend to stay farther apart from their cage mate and show fewer nose-to-nose contacts than controls
• in the isolation-induced ultrasonic vocalization test, pups separated from the mother emit an increased number of calls starting at P8
• at P55-P65, mice exhibit motor delay

skeleton
• 44% of mice display kyphosis
• fewer mice (25%) show kyphosis after 3 weeks of i.c.v. BCAA delivery

nervous system
N
• brain neurotransmitter levels (dopamine, serotonin, histamine) are normal
• EM imaging of somatosensory cortex layers 2-3 revealed a decreased area of GABAergic boutons and decreased density of vesicles per bouton
• the intensity of vesicular GABA transporter (VGAT) staining, a marker for GABAergic presynaptic terminals, is reduced in the somatosensory cortex
• however, protein levels the GABAergic postsynaptic marker neuroligin 2 are normal
• mice show a significant reduction of vesicle number in symmetric synapses in the somatosensory cortex
• mice show a significant reduction of vesicle number in symmetric synapses in the somatosensory cortex
• mice exhibit a significant cortical excitation and inhibition imbalance
• mice show a slight increase in the amplitude of mEPSCs in somatosensory cortex layers 2-3 pyramidal neurons
• mice show a marked reduction in the frequency of mIPSCs in somatosensory cortex layers 2-3 pyramidal neurons as well as in cerebellar Purkinje cells

cellular
• polysome profiling of brain cortical lysates showed a significant shift of ribosomes from actively translating polysomes toward the monosomal fraction, indicating decreased mRNA translation initiation in the brain

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
autism spectrum disorder DOID:0060041 J:238065


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
03/19/2024
MGI 6.23
The Jackson Laboratory