This gene has been identified with syndromic autism, where a subpopulation of individuals with a given syndrome develop autism. In particular, studies have found SLC9A6 variants to be identified with X-linked mental retardation and Angelman-like phenotypes. As well, mutation in the SLC9A6 gene has been identified with autism (Garbern et al., 2010).
Molecular Function
This gene encodes a sodium-hydrogen exchanger that is a member of the solute carrier family 9. The encoded protein may be involved in regulating endosomal pH and volume.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
A mutation affecting the sodium/proton exchanger, SLC9A6, causes mental retardation with tau deposition.
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
A lacZ cassette was inserted in exon 6 to inactivate the Slc9a6 gene, the endogenous gene promoter drives the expression of beta-galactosidase. Maintained in the mixed background, and maybe male or (-/y) or female (-/-) mice as Slc9a6 is on the X chromosome.
Allele Type: Targeted (knocout, reporter)
Strain of Origin: 129P2/OlaHsd
Genetic Background: 129P2/OlaHsd*C57BL/6
ES Cell Line: Mutant ES Cell Line: Model Source: JAX
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
A lacZ cassette was inserted to inactivate the Slc9a6 gene in exon6, the endogenous gene promoter drives the expression of beta-galactosidase. This line is bred to a pure C57bl/6 background.
Allele Type: Targeted (knocout, reporter)
Strain of Origin: 129P2/OlaHsd
Genetic Background: C57BL/6
ES Cell Line: Mutant ES Cell Line: Model Source: JAX
Model Type:
Genetic
Model Genotype:
Heterozygous
Mutation:
A lacZ cassette was inserted in exon 6 to inactivate the Slc9a6 gene, the endogenous gene promoter drives the expression of beta-galactosidase. Maintained in the mixed background and are female (-/+) mice as Slc9a6 is on the X chromosome.
Allele Type: Targeted (knocout, reporter)
Strain of Origin: 129P2/OlaHsd
Genetic Background: 129P2/OlaHsd*C57BL/6
ES Cell Line: Mutant ES Cell Line: Model Source: JAX
Description: Slc9a6 null males have a longer distance traveled and increased number of rears compared to wild type controls, indicating increase hyperactivity
Exp Paradigm: Males
Description: Slc9a6 null male mice have reduced motor coordination and balance in the balance beam test, determined by increased latency to cross beam and increased number of slips
Exp Paradigm: NA
Description: Slc9a6 null males have increased levels of hyperactivity in the open field test determined by increased distance traveled and number of rears
Exp Paradigm: Males
Description: There is a significant loss of purkinje cells in the cerebellum, occurring in a patterned manner in the vermis and hemispheres
Exp Paradigm: Males
Description: A significant loss of purkinje cells is seen in the anterior and posterior zones of the cerebellum, mostly in lobule i-ii
Exp Paradigm: Males
Description: Slc9a6 null male and female mice have a significant accumulation of the gm2 ganglioside in neurons from the ca3/ca4 region and the dentate gyrus of the hippocampus as well as the hypothalamus, fasciola cinereum and piriform cortex
Exp Paradigm: Males and females
Description: Slc9a6 null female mice have significant accumulation of the gm2 ganglioside in the neurons of the basolateral amygdala starting at 8 weeks itself
Exp Paradigm: Females
Description: Accumulation of gm2 ganglioside inside neurons from various parts of the brain, including the amygdala and ca3/ca4 hippocampal regions indicate significant dysfunction of the lysosomal degradation pathway for plasma membrane -attached lipids, in slc9a6 null male mice as well
Exp Paradigm: Males
Description: The hexosaminidase assay for beta hexosaminidase, the enzyme that degrades gm2 ganglioside conducted on brain tissue showed an absolute lack of enzyme activity in slc9a6 null mice
Exp Paradigm: NA
Description: There is an increase in the accumulation of hyperphosphorylated tau protein in the soluble fraction of the brain
Exp Paradigm: Males and females
Description: The number of synapses was reduced in slc9a6 null mice. they also had reduced number of mature synapses, both in basal dendrites and apical dendrites
Exp Paradigm: Golgi-cox stain was used to stain the hippocampus and the cortex
Description: Dendritic branching points and total number of branches are reduced in slc9a6 null mice, in the ca3 and ca1 regions of the hippocampus, compared to littermate controls
Exp Paradigm: Golgi-cox stain was used to stain the hippocampus and the cortex
Description: There is a significant (~25%) decrease in fiber volley amplitude in the hippocampal slices from slc9a6 null mice.
Exp Paradigm: Amplitude of the fiber volley was measured in the presence of ampar inhibitor
Description: There is a significant reduction in the total number of purkinje cells in the cerebellum of slc9a6 het female mice (but it is significantly less than what is observed in males)
Exp Paradigm: Females
Description: Accumulation of gm2 ganglioside inside neurons from various parts of the brain, including the amygdala and ca3/ca4 hippocampal regions indicate significant dysfunction of the lysosomal degradation pathway for plasma membrane -attached lipids, in slc9a6 het female mice
Exp Paradigm: Females
Description: Slc9a6 het females show no preference to the change in position of a previously encountered object, unlike wild type controls
Exp Paradigm: NA
