This gene has been identified with syndromic autism, where a subpopulation of individuals with a given syndrome develop autism. As well, rare variants in the SLC6A8 gene have been identified with autism (Po-Argelles et al., 2006).
Molecular Function
The encoded protein has creatine:sodium symporter activity.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
X-Linked creatine transporter deficiency in two patients with severe mental retardation and autism.
Longitudinal analysis of behavior in creatinine deficiency syndrome modeled in the SLC6A8 hemizygous knockout mice show progressive impairment of short and long-term declarative memory indicating abnormally early aging of the brain. Pathological examinations of SLC6A8 hemizygous knockout mice show loss of GABAergic synapses, marked activation of microglia, reduction of hippocampal neurogenesis and accumulation of autofluorescent lipofucsin.
References
Type
Title
Author, Year
Primary
A mouse model for creatine transporter deficiency reveals early onset cognitive impairment and neuropathology associated with brain aging.
Model Type:
Genetic
Model Genotype:
Hemizygous
Mutation:
Male mice with one allele of Slc6A8 knocked out were generated by FLP/CRE recombination by introducing loxP sites flanking exon 57 of the gene in embryonic stem cells. As CrT deficiency is an X-linked pathology male mice were selected for this study.
Allele Type: Targeted(knockout)
Strain of Origin: C57BL/6 J
Genetic Background: C57BL/6 J
ES Cell Line: Unreported
Mutant ES Cell Line: Unreported
Model Source: Unreported
Model Type:
Genetic
Model Genotype:
Hemizygous
Mutation:
Conditional deletion of exon 27 of Slc6a8 gene using Nestin-cre, in neuronal, glial and other cell types including blood brain barrier endothelial cells, in the central and peripheral nervous system. As creatine transporter deficiency is an X-linked pathology, male mice were selected for this study.
Allele Type: Conditional loss-of-function
Strain of Origin: C57BL/6 J
Genetic Background: C57BL/6 J
ES Cell Line: 129/Sv* C57BL/6N
Mutant ES Cell Line: Unreported
Model Source: Unreported
Description: Slc6a8 hemizygous mice show decreased number of neuronal precursors in the hippocampal dentate gyrus compared to controls
Exp Paradigm: Male only
Description: Slc6a8 hemizygous mice show decreased inhibitory synapses in all layers of the pfc and acc, compared to controls
Exp Paradigm: Prefrontal cortex and anterior cingulate cortex examined, male only
Description: Slc6a8 hemizygous mice show decreased creatinine levels in the cerebral cortex and hippocampus compared to controls
Exp Paradigm: Male only
Description: Slc6a8 hemizygous mice show increased guanidinoacetic acid (gaa) in the brain, particularly the hippocampus, and muscle compared to wildtype controls
Exp Paradigm: Male only
Description: Slc6a8 hemizygous mice show increased number of activated microglia and a corresponding decrease in resting microglia compared to controls
Exp Paradigm: Prefrontal cortex and anterior cingulate cortex examined, male only
Description: Slc6a8 hemizygous mice could not remember the location of the platform and explored all quadrants equally whereas control mice spent more time in the quadrant where the platform was located during training
Exp Paradigm: Males only
Description: Slc6a8 hemizygous mice show a decrease in the number of spontaneous alternations of entries into the arms compared to controls
Exp Paradigm: Male only, y-maze test spontaneous alternation
Description: During probe trial in the mwm, slc6a8 hemizygous mice explored the four quadrants of the maze for the missing platform while control animals spent significantly longer time in the quadrant where the platform was located during the training days
Exp Paradigm: During probe trial the escape platform was removed from the tank and the swimming paths were recorded over 60 s while mice searched for the missing platform
Description: Slc6a8 cko hemizygous mice show decreased number of total dividing cells in the dentate gyrus compared to controls
Exp Paradigm: Male only
Description: Slc6a8 cko hemizygous mice show decreased creatinine levels in the brain compared to controls, slc6a8 cko hemizygous mice show no change in creatine levels in peripheral tissues, animals not expressing cre recombinase did not show a hypomorph phenotype, with normal levels of cr in different tissues
Exp Paradigm: Male only
Description: Slc6a8 cko hemizygous mice show decreased guanidinoacetic acid (gaa) in the brain compared to controls, slc6a8 cko hemizygous mice show no change in guanidinoacetic acid (gaa) in peripheral tissues
Exp Paradigm: Male only
Description: Slc6a8 cko hemizygous mice show decreased long-term object recognition at 24 hours, compared to controls, at 4 weeks, 2, 3.4 and 6 months
Exp Paradigm: Male only
Description: Slc6a8 cko hemizygous mice show a decrease in the number of spontaneous alternations of entries into the arms compared to controls
Exp Paradigm: Male only, y maze spontaneous alternation
