Defective forebrain development in mice lacking gp330/megalin

Thomas E. Willnow, Jan Hilpert, Scott A. Armstrong, Astrid Rohlmann, Robert E Hammer, Dennis K Burns, Joachim Herz

Research output: Contribution to journalArticle

382 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)8460-8464
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume93
Issue number16
DOIs
StatePublished - Aug 6 1996

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Low Density Lipoprotein Receptor-Related Protein-2
Prosencephalon
Epithelium
Lipoprotein Receptors
LDL Receptors
Olfactory Bulb
Knockout Mice
Respiratory Insufficiency
Lipoproteins
Peptide Hydrolases
Cholesterol
Mothers
Kidney
Food
Lung
Brain
Genes
Proteins

Keywords

  • apoB
  • cholesterol
  • lipoprotein transport
  • plasminogen activation

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Defective forebrain development in mice lacking gp330/megalin. / Willnow, Thomas E.; Hilpert, Jan; Armstrong, Scott A.; Rohlmann, Astrid; Hammer, Robert E; Burns, Dennis K; Herz, Joachim.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 93, No. 16, 06.08.1996, p. 8460-8464.

Research output: Contribution to journalArticle

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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.

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