Expression of Kinase Interacting with Stathmin (KIS, UHMK1) in human brain and lymphoblasts: effects of schizophrenia and genotype

Greg C. Bristow, Tracy A. Lane, Mary Walker, Li Chen, Yoshi Sei, Thomas M. Hyde, Joel E. Kleinman, Paul J. Harrison, Sharon L. Eastwood

Research output: Contribution to journalArticle

Abstract

Single nucleotide polymorphisms (SNPs) within the gene encoding the serine/threonine kinase KIS (Kinase Interacting with Stathmin, also known as UHMK1) have recently been associated with schizophrenia. As none of the disease associated SNPs are coding, they may confer susceptibility by altering some facet of KIS expression. Here we have characterised the cellular distribution of KIS in human brain using in situ hybridisation and immunohistochemistry, and quantified KIS protein and mRNA in two large brain series to determine if KIS expression is altered in schizophrenia or bipolar disorder or in relation to a schizophrenia-associated SNP (rs7513662). Post-mortem tissue from the superior temporal gyrus of schizophrenia and control subjects, and also dorsolateral prefrontal cortex, anterior cingulate cortex, and cerebellum from schizophrenia, bipolar disorder, and control subjects were used. KIS expression was measured by quantitative PCR (mRNA) and immunoautoradiography (protein), and was also quantified by immunoblot in lymphoblast cell lines derived from schizophrenia and control subjects. Our results demonstrate that KIS is expressed in neurons, and its encoded protein is localised to the nucleus and cytoplasm. No difference in KIS expression was found between diagnostic groups, or in the lymphoblast cell lines, and no effect of rs7513662 genotype on KIS expression was found. Hence, these data do not provide support for the hypothesis that altered expression is the mechanism by which genetic variation of KIS may increase susceptibility to schizophrenia, nor evidence that KIS expression is altered in the disease itself, at least in terms of the parameters studied here.

Original languageEnglish (US)
Pages (from-to)197-206
Number of pages10
JournalBrain research
Volume1301
DOIs
StatePublished - Nov 16 2009
Externally publishedYes

Keywords

  • Bipolar disorder
  • Gene expression
  • Psychosis
  • Schizophrenia
  • UHMK1

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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