Housekeeping gene xanthine oxidoreductase is necessary for milk fat droplet enveloping and secretion: gene sharing in the lactating mammary gland.

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Publication Type Journal Article
School or College College of Science; School of Medicine
Department Oncological Sciences; Biology; Human Genetics
Program Institute of Human Genetics; Howard Hughes Medical Institute (HHMI)
Creator Capecchi, Mario R.
Other Author Vorbach, Claudia; Scriven, Alistair
Title Housekeeping gene xanthine oxidoreductase is necessary for milk fat droplet enveloping and secretion: gene sharing in the lactating mammary gland.
Date 2002-12-15
Description Xanthine oxidoreductase (XOR) is the rate-limiting enzyme in purine catabolism occurring in most cell types. However, this housekeeping gene is expressed at very high levels in a number of mammalian tissues including the lactating mammary epithelium, suggesting additional roles for XOR in these tissues. Mice with targeted disruption of XOR were generated to assess these potential additional roles. XOR-/- mice are runted and do not live beyond 6 wk of age. Strikingly, however, XOR+/- females, although of healthy appearance and normal fertility, are unable to maintain lactation and their pups die of starvation 2 wk postpartum. Histological and whole-mount analyses showed that in XOR+/- females the mammary epithelium collapses, resulting in premature involution of the mammary gland. Electron microscopy showed that XOR is specifically required for enveloping milk fat droplets with the apical plasma membrane prior to secretion from the lactating mammary gland. We present evidence that XOR may have primarily a structural role, as a membrane-associated protein, in milk fat droplet secretion and thus XOR provides another example of "gene sharing". About 5% of women experience primary lactation insufficiency. The above observations suggest that human females suffering from xanthinuria, a deficiency in XOR, are potential candidates for lactation problems.
Type Text
Publisher Cold Spring Harbor Lab Press
Volume 16
Issue 24
First Page 3223
Last Page 3235
Subject Body Weight; Cell Differentiation; Cell Membrane; Epithelium
Subject MESH Glycolipids; Glycoproteins; Lactation; Mammary Glands, Animal; Xanthine Oxidase
Language eng
Bibliographic Citation Genes Dev. 2002 Dec 15;16(24):3223-35.: Vorbach C, Scriven A, Capecchi MR. The housekeeping gene xanthine oxidoreductase is necessary for milk fat droplet enveloping and secretion: gene sharing in the lactating mammary gland. Retrieved on September 15.2006 from http://www.genesdev.org/cgi/content/full/16/24/3223.
Rights Management Copyright 2004 Cold Spring Harbor Laboratory Press. All Rights Reserved.
Format Medium application/pdf
Identifier ir-main,409
ARK ark:/87278/s6mp5mqr
Setname ir_uspace
ID 705717
Reference URL https://collections.lib.utah.edu/ark:/87278/s6mp5mqr
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