TY - JOUR
T1 - Defective forebrain development in mice lacking gp330/megalin
AU - Willnow, Thomas E.
AU - Hilpert, Jan
AU - Armstrong, Scott A.
AU - Rohlmann, Astrid
AU - Hammer, Robert E
AU - Burns, Dennis K
AU - Herz, Joachim
PY - 1996/8/6
Y1 - 1996/8/6
N2 - gp330/megalin, a member of the low density lipoprotein (LDL) receptor gene family, is expressed on the apical surfaces of epithelial tissues, including the neuroepithelium, where it mediates the endocytic uptake of diverse macromolecules, such as cholesterol-carrying lipoproteins, proteases, and antiproteinases. Megalin knockout mice manifest abnormalities in epithelial tissues including lung and kidney that normally express the protein and they die perinatally from respiratory insufficiency. In brain, impaired proliferation of neuroepithelium produces a holoprosencephalic syndrome, characterized by lack of olfactory bulbs, forebrain fusion, and a common ventricular system. Similar syndromes in humans and animals are caused by insufficient supply of cholesterol during development. Because megalin can bind lipoproteins, we propose that the receptor is part of the maternal- fetal lipoprotein transport system and mediates the endocytic uptake of essential nutrients in the postgastrulation stage.
AB - gp330/megalin, a member of the low density lipoprotein (LDL) receptor gene family, is expressed on the apical surfaces of epithelial tissues, including the neuroepithelium, where it mediates the endocytic uptake of diverse macromolecules, such as cholesterol-carrying lipoproteins, proteases, and antiproteinases. Megalin knockout mice manifest abnormalities in epithelial tissues including lung and kidney that normally express the protein and they die perinatally from respiratory insufficiency. In brain, impaired proliferation of neuroepithelium produces a holoprosencephalic syndrome, characterized by lack of olfactory bulbs, forebrain fusion, and a common ventricular system. Similar syndromes in humans and animals are caused by insufficient supply of cholesterol during development. Because megalin can bind lipoproteins, we propose that the receptor is part of the maternal- fetal lipoprotein transport system and mediates the endocytic uptake of essential nutrients in the postgastrulation stage.
KW - apoB
KW - cholesterol
KW - lipoprotein transport
KW - plasminogen activation
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U2 - 10.1073/pnas.93.16.8460
DO - 10.1073/pnas.93.16.8460
M3 - Article
C2 - 8710893
AN - SCOPUS:0029775625
SN - 0027-8424
VL - 93
SP - 8460
EP - 8464
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 16
ER -