TY - JOUR
T1 - Disruption of hedgehog signaling reveals a novel role in intestinal morphogenesis and intestinal-specific lipid metabolism in mice
AU - Wang, Li Chun
AU - Nassir, Fatiha
AU - Liu, Zhong Ying
AU - Ling, Leona
AU - Kuo, Frank
AU - Crowell, Thomas
AU - Olson, Dian
AU - Davidson, Nicholas O.
AU - Burkly, Linda C.
N1 - Funding Information:
Supported in part by National Institutes of Health grants DK 56260 and DK52574 (to F.N. and N.O.D.).
PY - 2002/2
Y1 - 2002/2
N2 - Background & Aims: The hedgehog (hh) signaling pathway has been shown to play crucial roles in the development of embryonic gut. However, its role in intestinal development and function beyond the embryonic stage is still undefined. Methods: Expression of hh and its receptor, Patched, were examined by Western blot and X-gal staining. An anti-hh monoclonal antibody was administered into developing embryos or postnatal mice and histologic analyses were performed. Effects on lipid metabolism were examined by Oil Red O and Sudan III stainings, messenger RNA (mRNA) analysis, and electron microscopy. Serum apolipoprotein IV level, a marker for lipid absorption, was quantified by Western blot. Results: Mice receiving anti-hh monoclonal antibody in utero or after birth exhibited progressive runting and died before weaning. Histology revealed hyperproliferation of intestinal crypt epithelial cells and disorganization of the villi with prominent vacuolation and accumulation of neutral lipid. Fecal fat microscopy revealed numerous large fat droplets. Intestinal mRNA abundance of 2 candidate genes involved in lipid transport, mtp and apob, was unchanged, although serum levels of apolipoprotein A-IV were reduced. Conclusions: Abnormal villus structure, lipid-filled enterocytes, and fatty stools in anti-hh monoclonal antibody-treated mice indicate a novel role for hh signaling in intestinal morphogenesis and lipid transport in postnatal mice.
AB - Background & Aims: The hedgehog (hh) signaling pathway has been shown to play crucial roles in the development of embryonic gut. However, its role in intestinal development and function beyond the embryonic stage is still undefined. Methods: Expression of hh and its receptor, Patched, were examined by Western blot and X-gal staining. An anti-hh monoclonal antibody was administered into developing embryos or postnatal mice and histologic analyses were performed. Effects on lipid metabolism were examined by Oil Red O and Sudan III stainings, messenger RNA (mRNA) analysis, and electron microscopy. Serum apolipoprotein IV level, a marker for lipid absorption, was quantified by Western blot. Results: Mice receiving anti-hh monoclonal antibody in utero or after birth exhibited progressive runting and died before weaning. Histology revealed hyperproliferation of intestinal crypt epithelial cells and disorganization of the villi with prominent vacuolation and accumulation of neutral lipid. Fecal fat microscopy revealed numerous large fat droplets. Intestinal mRNA abundance of 2 candidate genes involved in lipid transport, mtp and apob, was unchanged, although serum levels of apolipoprotein A-IV were reduced. Conclusions: Abnormal villus structure, lipid-filled enterocytes, and fatty stools in anti-hh monoclonal antibody-treated mice indicate a novel role for hh signaling in intestinal morphogenesis and lipid transport in postnatal mice.
UR - http://www.scopus.com/inward/record.url?scp=0036165339&partnerID=8YFLogxK
U2 - 10.1053/gast.2002.31102
DO - 10.1053/gast.2002.31102
M3 - Article
C2 - 11832461
AN - SCOPUS:0036165339
SN - 0016-5085
VL - 122
SP - 469
EP - 482
JO - Gastroenterology
JF - Gastroenterology
IS - 2
ER -