Faculty Research 1980 - 1989

The human and rodent intestinal fatty acid binding protein genes. A comparative analysis of their structure, expression, and linkage relationships.

Document Type

Article

Publication Date

1987

Keywords

Animal, Base-Sequence, Carrier-Proteins: ge, Chromosome-Mapping, Chromosomes-Human-Pair-2, Chromosomes-Human-Pair-4, Comparative-Study, DNA-Restriction-Enzymes, Genes-Structural, Human, Intestine-Small: me, Linkage-(Genetics), Liver: me, Mice, Molecular-Sequence-Data, Species-Specificity, SUPPORT-NON-U-S-GOVT, SUPPORT-U-S-GOVT-P-H-S, Transcription-Genetic

First Page

16060

Last Page

16071

JAX Source

J-Biol-Chem. 1987 Nov 25; 262(33):16060-71.

Grant

DK30292, DK37960, HL27481

Abstract

Intestinal fatty acid binding protein (I-FABP) is believed to participate in the uptake, intracellular metabolism, and/or transport of long chain fatty acids within enterocytes. The 15.1-kDA rodent proteins is a member of a family of low Mr cytoplasmic proteins that have evolved to bind different ligands. We have now determined the nucleotide sequence of the gene encoding human I-FABP and defined the primary structure of its protein product. The human I-FABP gene spans 3382 nucleotides and contains 4 exons (103 or 128, 173, 108, and 312 base pairs). interrupted by 3 introns (1194, 1023, and 444 base pairs). The 132-residue rat and human I-FABPs have 82% amino acid sequence identity. Blot hybridization studies of RNAs prepared from a variety of adult rhesus monkey tissues as well as human intestine and liver indicate that I-FABP mRNA is confined to the intestine. I-FABP mRNA was not detectable in a number of cultured human enterocyte-like cell lines, suggesting it may be a sensitive marker for differentiated, villus-associated, small intestinal lining cells. Given the similar patterns of tissue-specific expression exhibited by the rat and human genes, we compared their 5' nontranscribed regions. Optimal alignments of the two sequences disclosed 64% identity among the 260 nucleotides immediately 5' to the start site of transcription. Matrix plots revealed a 14-nucleotide long repeated sequence (5'-TGAACTTTGAACTT-3') in the 5' nontranscribed region of both genes as well as in a comparable region of another family member that is expressed in enterocytes, cellular retinol binding protein II. The linkage relationships between I-FABP and the homologous liver FABP (L-FABP) gene were defined in mice and humans. The mouse genes were mapped using restriction fragment length polymorphisms and recombinant inbred strains. The I-FABP gene is located on mouse chromosome 3 between the amylase 1,2 (Amy 1,2) and alcohol dehydrogenase 3 (Adh-3) loci while the L-FABP gene is on mouse chromosome 6 within 3 centimorgans of the lymphocyte antigen-2 (Ly-2) locus. Mouse L-FABP may be identical to the major liver protein-1 (Lvp-1) which is encoded by a gene situated within a centimorgan of Ly-2. Human gene mapping studies were carried out using a panel of mouse-human somatic cell hybrid clones as well as in situ hybridization to metaphase chromosomes.(ABSTRACT TRUNCATED AT 400 WORDS)

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