Alu-splice cloning of human Intersectin (ITSN), a putative multivalent binding protein expressed in proliferating and differentiating neurons and overexpressed in Down syndrome

C. Pucharcos, J. J. Fuentes, C. Casas, S. De la Luna, S. Alcantara, M. L. Arbones, E. Soriano, X. Estivill, M. Pritchard

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Abstract

By Alu-splice PCR we have trapped two exons and subsequently identified the full length cDNA of a human gene, Intersectin (ITSN), which maps to chromosome 21q22.1 between markers D21S320 and D21S325. The gene has the potential to code for at least two different protein isoforms by alternative splicing (ITSN-L and ITSN-S). Intersectin exists with a high degree of similarity in flies, frogs and mammals, suggesting a conserved role in higher eukaryotes. Analysis of the expression pattern of human and mouse Intersectin detected mRNAs in all adult and foetal tissues tested, with the longer isoform present in brain. In situ hybridisation studies in the developing mouse brain showed ITSN expression in both proliferating and differentiating neurons. The genomic structure of ITSN was determined using the chromosome 21 sequences deposited in the public databases. The protein contains several known motifs which implicate ITSN in clathrin mediated endocytosis and synaptic vesicle recycling. The expression pattern of Intersectin in mouse brain, its presumed function and its overexpression in brains from Down syndrome patients, suggest that Intersectin may contribute in a gene dosage-dependent manner to some of the abnormalities of Down syndrome.

Original languageEnglish
Pages (from-to)704-712
Number of pages9
JournalEuropean Journal of Human Genetics
Volume7
Issue number6
DOIs
Publication statusPublished - 17 Sep 1999

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Keywords

  • Chromosome 21q22
  • Down syndrome
  • Endocytosis
  • Intersectin

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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