Abstract

The RNAs encoding two long fatty acid binding proteins (FABPs) are among the most abundant species which accumulate in the small intestinal lining cells (enterocytes) of rodents and man. These proteins (termed liver and intestinal FABP based on their initial sites of isolation) are members of a family of 8 small (14- 16 kDa) cytosolic polypeptides which bind hydrophobic ligands. Although their precise physiologic roles have not been defined, the two FABPs are most likely involved in the uptake, intracellular compartmentalization or metabolism of their ligands. We will use these FABPs as models to (i) define the molecular basis of fatty acid-protein interaction and (ii) identify cis acting elements which confer gastrointestinal specific gene expression. To achieve the first specific aim we will continue our crystallographic studies of rat intestinal FABP purified from E. coli containing a suitably constructed prokaryotic expression vector. Mapping studies will involve fusion of different portions of the 5' nontranscribed regions of the I and L-FABP genes to the human growth hormone structural gene, creation of transgenic mice and analysis of hGH gene expression in various murine tissues by RNA blot hybridization and immunocytochemical localization studies.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK030292-09
Application #
3229361
Study Section
Molecular Cytology Study Section (CTY)
Project Start
1982-01-01
Project End
1992-12-31
Budget Start
1990-01-01
Budget End
1990-12-31
Support Year
9
Fiscal Year
1990
Total Cost
Indirect Cost

  Institution

Name
Washington University
Department
Type
Schools of Medicine
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130

  Publications

Thackray, Larissa B; Handley, Scott A; Gorman, Matthew J et al. (2018) Oral Antibiotic Treatment of Mice Exacerbates the Disease Severity of Multiple Flavivirus Infections. Cell Rep 22:3440-3453.e6
Mark Welch, Jessica L; Hasegawa, Yuko; McNulty, Nathan P et al. (2017) Spatial organization of a model 15-member human gut microbiota established in gnotobiotic mice. Proc Natl Acad Sci U S A 114:E9105-E9114
Spaulding, Caitlin N; Klein, Roger D; Ruer, Ségolène et al. (2017) Selective depletion of uropathogenic E. coli from the gut by a FimH antagonist. Nature 546:528-532
Cervantes-Barragan, Luisa; Chai, Jiani N; Tianero, Ma Diarey et al. (2017) Lactobacillus reuteri induces gut intraepithelial CD4+CD8??+ T cells. Science 357:806-810
Ma, Huijuan; Sales, Vicencia M; Wolf, Ashley R et al. (2017) Attenuated Effects of Bile Acids on Glucose Metabolism and Insulin Sensitivity in a Male Mouse Model of Prenatal Undernutrition. Endocrinology 158:2441-2452
Hibberd, Matthew C; Wu, Meng; Rodionov, Dmitry A et al. (2017) The effects of micronutrient deficiencies on bacterial species from the human gut microbiota. Sci Transl Med 9:
Griffin, Nicholas W; Ahern, Philip P; Cheng, Jiye et al. (2017) Prior Dietary Practices and Connections to a Human Gut Microbial Metacommunity Alter Responses to Diet Interventions. Cell Host Microbe 21:84-96
Charbonneau, Mark R; O'Donnell, David; Blanton, Laura V et al. (2016) Sialylated Milk Oligosaccharides Promote Microbiota-Dependent Growth in Models of Infant Undernutrition. Cell 164:859-71
Wagner, Vitas E; Dey, Neelendu; Guruge, Janaki et al. (2016) Effects of a gut pathobiont in a gnotobiotic mouse model of childhood undernutrition. Sci Transl Med 8:366ra164
Planer, Joseph D; Peng, Yangqing; Kau, Andrew L et al. (2016) Development of the gut microbiota and mucosal IgA responses in twins and gnotobiotic mice. Nature 534:263-6

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