title: SLC9A9 mutations, gene expression, and protein-protein interactions in rat models of attention-deficit/hyperactivity disorder.
abstract: SLC9A9 (solute carrier family 9, member 9, also known as Na+/H+ exchanger member (NHE9)) is a membrane protein that regulates the luminal pH of the recycling endosome, an essential organelle for synaptic transmission and plasticity. SLC9A9 has been implicated in human attention deficit hyperactivity disorder (ADHD) and in rat studies of hyperactivity. We examined the SLC9A9 gene sequence and expression profile in prefrontal cortex, dorsal striatum and hippocampus in two genetic rat models of ADHD. We report two mutations in a rat model of inattentive ADHD, the WKY/NCrl rat, which affect the interaction of SLC9A9 with calcineurin homologous protein (CHP). We observed an age-dependent abnormal expression of SLC9A9 in brains of this inattentive model and in the Spontaneous Hypertensive Rat (SHR) model of ADHD. Our data suggest a novel mechanism whereby SLC9A9 sequence variants and abnormalities in gene expression could contribute to the ADHD-like symptoms of rat models and possibly the pathophysiology of ADHD in humans.
authors.affiliation: Department of Psychiatry, SUNY Upstate Medical University, Syracuse, New York, USA.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Zhang-James
authors.forename: Tania
authors.initials: T
authors.lastname: DasBanerjee
authors.forename: Terje
authors.initials: T
authors.lastname: Sagvolden
authors.forename: Frank A
authors.initials: FA
authors.lastname: Middleton
authors.forename: Stephen V
authors.initials: SV
authors.lastname: Faraone
mesh_terms: D000818:Animals; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics* / Q000378:metabolism*; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D047468:Immunoprecipitation; D009154:Mutation / Q000235:genetics*; D011485:Protein Binding / Q000235:genetics; D060066:Protein Interaction Maps / Q000235:genetics*; D051381:Rats; D011922:Rats, Mutant Strains; D017923:Sodium-Hydrogen Exchangers / Q000235:genetics* / Q000378:metabolism; D016708:Synaptophysin / Q000235:genetics
chemical_list: C569285:Slc9a9 protein, rat; D017923:Sodium-Hydrogen Exchangers; D016708:Synaptophysin