title: Intersectin 1 contributes to phenotypes in vivo: implications for Down's syndrome.
abstract: Intersectin 1 (ITSN1) is a human chromosome 21 (HSA21) gene product encoding a multidomain scaffold protein that functions in endocytosis, signal transduction, and is implicated in Down's syndrome, Alzheimer's Disease, and potentially other neurodegenerative diseases through activation of c-Jun N-terminal kinase. We report for the first time that ITSN1 proteins are elevated in individuals with Down's syndrome of varying ages. However, ITSN1 levels decreased in aged cases with Down's syndrome with Alzheimer's disease-like neuropathology. Analysis of a novel ITSN1 transgenic mouse reveals that ITSN1 overexpression results in a sex-dependent decrease in locomotor activity. This study reveals a link between overexpression of specific ITSN1 isoforms and behavioral phenotypes and has implications for human neurodegenerative diseases such as Down's syndrome and Alzheimer's disease.
authors.affiliation: Department of Pharmacology, University of Illinois College of Medicine, Chicago, Illinois 60612, USA.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Hunter
authors.forename: Marianela
authors.initials: M
authors.lastname: Nelson
authors.forename: Michael
authors.initials: M
authors.lastname: Kurzer
authors.forename: Xuerong
authors.initials: X
authors.lastname: Wang
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Kryscio
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Head
authors.forename: Graziano
authors.initials: G
authors.lastname: Pinna
authors.forename: John P
authors.initials: JP
authors.lastname: O'Bryan
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000096:biosynthesis*; D000293:Adolescent; D000328:Adult; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D004195:Disease Models, Animal; D004314:Down Syndrome / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D009043:Motor Activity / Q000502:physiology*; D010641:Phenotype; D055815:Young Adult
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; C485568:ITSN1 protein, human