Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/122321
Title: THE ROLE OF FAT-STORAGE INDUCING TRANSMEMBRANE PROTEIN 2 (FITM2) IN MAMMALIAN PHYSIOLOGY AND DISEASE
Authors: GOH JIN-LING, VERA
Keywords: lipid droplet, intestinal malabsorption, neuropathy
Issue Date: 6-Nov-2015
Source: GOH JIN-LING, VERA (2015-11-06). THE ROLE OF FAT-STORAGE INDUCING TRANSMEMBRANE PROTEIN 2 (FITM2) IN MAMMALIAN PHYSIOLOGY AND DISEASE. ScholarBank@NUS Repository.
Abstract: Lipid droplets (LDs) are phylogenetically conserved cytoplasmic organelles that store neutral lipids within a phospholipid monolayer. Fat storage inducing transmembrane protein 2 (FIT2/FITM2) is a ubiquitously expressed transmembrane endoplasmic reticulum (ER) protein that has previously been implicated in LD formation in mammalian cells and tissues. FIT2 null human patients are described for the first time in this thesis to have progressive paraparesis, deafness, and histopathological evidence of decreased myelinated fiber density and pronounced myelin abnormalities. The tamoxifen-inducible ROSA26CreERT2-mediated whole body FIT2 knockout mouse (iF2KO) was generated to study the metabolic effects of FIT2 deletion at the whole organism level. We showed that tamoxifen-induced FIT2 deletion using the iF2KO mouse model led to lethal intestinal pathology including villus blunting and death of intestinal crypts. At the cellular level, LDs failed to form in iF2KO enterocytes after acute oil challenge, and neutral lipid instead accumulated within the ER. Intestinal bile acid transporters were transcriptionally dysregulated in iF2KO mice, leading to the buildup of bile acids within enterocytes. These data support the conclusion that FIT2 plays an essential role in regulating intestinal health and survival postnatally in mice.
URI: http://scholarbank.nus.edu.sg/handle/10635/122321
Appears in Collections:Ph.D Theses (Open)

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