Intersectin 1 contributes to phenotypes in vivo: implications for Down Syndrome

Abstract

Intersectin 1 (ITSN1) is a chromosome 21 (HSA21) gene product encoding a multidomain scaffold protein that functions in endocytosis, signal transduction and is implicated in Down Syndrome, Alzheimer’s Disease, and potentially other neurodegenerative diseases through activation of c-Jun N-terminal kinase (JNK). We report for the first time that ITSN1 proteins are elevated in Down Syndrome individuals of varying ages. However, ITSN1 levels decreased in aged Down Syndrome cases 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 Syndrome and Alzheimer’s Disease.