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Molecular and Cellular Biology, November 2003, p. 7525-7530, Vol. 23, No. 21
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.21.7525-7530.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Accelerated Fat Absorption in Intestinal Alkaline Phosphatase Knockout Mice{dagger}

Sonoko Narisawa,1 Lei Huang,1 Arata Iwasaki,1 Hideaki Hasegawa,2 David H. Alpers,3 and José Luis Millán1*

The Burnham Institute, La Jolla, California 92037,1 Laboratories for Structure and Function Research, Tokai University School of Medicine, Kanagawa, Japan,2 Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 631103

Received 5 February 2003/ Returned for modification 10 April 2003/ Accepted 23 July 2003

Intestinal alkaline phosphatase (IAP) is the most ancestral of the tissue-specific members of the AP gene family. Several studies have suggested an absorptive function for IAP, but in vivo data to this effect have been lacking. We inactivated the mouse IAP gene in embryo-derived stem cells and generated mice homozygous for the null mutation. The mice were macroscopically and histologically normal and fertile and showed no difference from the wild-type controls under normal laboratory conditions. However, when maintained long-term on a high-fat diet, the IAP-deficient mice showed faster body weight gain than did control animals. Histological examination revealed an accelerated transport of fat droplets through the intestinal epithelium and elevation of serum triglyceride levels in the IAP-deficient mice compared to wild-type mice. Our study suggests that IAP participates in a rate-limiting step regulating fat absorption.

* Corresponding author. Mailing address: The Burnham Institute, 10901 North Torrey Pines Rd., La Jolla, CA 92037. Phone: (858) 646-3130. Fax: (858) 713-6272. E-mail: millan{at}burnham.org.

{dagger} This paper is dedicated to the memory of the late Keiichi Watanabe (1934 to 2002), Tokai University, Kanagawa, Japan, for his pioneering work on IAP and for his interest and encouragement during the course of this work.

Molecular and Cellular Biology, November 2003, p. 7525-7530, Vol. 23, No. 21
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.21.7525-7530.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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