%0 Journal Article
%T Carnitine Deficiency in OCTN2£¿/£¿ Newborn Mice Leads to a Severe Gut and Immune Phenotype with Widespread Atrophy, Apoptosis and a Pro-Inflammatory Response
%A Srinivas Sonne
%A Prem S. Shekhawat
%A Dietrich Matern
%A Vadivel Ganapathy
%A Leszek Ignatowicz
%J PLOS ONE
%D 2012
%I Public Library of Science (PLoS)
%R 10.1371/journal.pone.0047729
%X We have investigated the gross, microscopic and molecular effects of carnitine deficiency in the neonatal gut using a mouse model with a loss-of-function mutation in the OCTN2 (SLC22A5) carnitine transporter. The tissue carnitine content of neonatal homozygous (OCTN2£¿/£¿) mouse small intestine was markedly reduced; the intestine displayed signs of stunted villous growth, early signs of inflammation, lymphocytic and macrophage infiltration and villous structure breakdown. Mitochondrial ¦Â-oxidation was active throughout the GI tract in wild type newborn mice as seen by expression of 6 key enzymes involved in ¦Â-oxidation of fatty acids and genes for these 6 enzymes were up-regulated in OCTN2£¿/£¿ mice. There was increased apoptosis in gut samples from OCTN2£¿/£¿ mice. OCTN2£¿/£¿ mice developed a severe immune phenotype, where the thymus, spleen and lymph nodes became atrophied secondary to increased apoptosis. Carnitine deficiency led to increased expression of CD45-B220+ lymphocytes with increased production of basal and anti-CD3-stimulated pro-inflammatory cytokines in immune cells. Real-time PCR array analysis in OCTN2£¿/£¿ mouse gut epithelium demonstrated down-regulation of TGF-¦Â/BMP pathway genes. We conclude that carnitine plays a major role in neonatal OCTN2£¿/£¿ mouse gut development and differentiation, and that severe carnitine deficiency leads to increased apoptosis of enterocytes, villous atrophy, inflammation and gut injury.
%U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0047729