Identification of a mutation in the ileal sodium-dependent bile acid transporter gene that abolishes transport activity

Melissa Wong, P. Oelkers, P. A. Dawson

Research output: Contribution to journalArticle

179 Citations (Scopus)

Abstract

The ileal Na+/bile acid cotransporter plays a critical role in the reabsorption of bile acids from the small intestine. In the course of cloning and characterizing the human ileal Na+/bile acid cotransporter cDNA, a dysfunctional isoform was identified in a patient diagnosed with Crohn's disease. Expression studies using hamster-human ileal Na+/bile acid cotransporter cDNA chimeras narrowed the location of the defect to the carboxyl-terminal 94 amino acids. Comparison of the sequence of the dysfunctional isoform to that of a wild-type human ileal Na+/bile acid cotransporter genomic clone revealed a single C to T transition resulting in a proline to serine substitution at amino acid position 290. The inheritance of this mutation in the proband's family was confirmed by single-stranded conformation polymorphism analysis and DNA sequencing. In transfected COS-1 cells, the single amino acid change abolished taurocholate transport activity but did not alter the transporter's synthesis or subcellular distribution. This dysfunctional mutation represents the first known molecular defect in a human sodium-dependent bile acid transporter.

Original languageEnglish (US)
Pages (from-to)27228-27234
Number of pages7
JournalJournal of Biological Chemistry
Volume270
Issue number45
DOIs
StatePublished - 1995
Externally publishedYes

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Genes
Mutation
Amino Acids
Protein Isoforms
Complementary DNA
Taurocholic Acid
Defects
Cloning
COS Cells
Amino Acid Substitution
Polymorphism
Bile Acids and Salts
DNA Sequence Analysis
Proline
Crohn Disease
Cricetinae
Serine
Small Intestine
Conformations
Organism Cloning

ASJC Scopus subject areas

  • Biochemistry

Cite this

Identification of a mutation in the ileal sodium-dependent bile acid transporter gene that abolishes transport activity. / Wong, Melissa; Oelkers, P.; Dawson, P. A.

In: Journal of Biological Chemistry, Vol. 270, No. 45, 1995, p. 27228-27234.

Research output: Contribution to journalArticle

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