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Molecular and Cellular Biology, July 2000, p. 5208-5215, Vol. 20, No. 14
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Fatal Bilateral Chylothorax in Mice Lacking the Integrin alpha 9beta 1

X. Z. Huang,1,2 J. F. Wu,1,2 R. Ferrando,1,2 J. H. Lee,1,2 Y. L. Wang,1,2 R. V. Farese Jr.,2,3 and D. Sheppard1,2,*

Lung Biology Center, Center for Occupational and Environmental Health, Cardiovascular Research Institute,1 and Department of Medicine,2 University of California, San Francisco, and Gladstone Institute of Cardiovascular Disease,3 San Francisco, California

Received 29 February 2000/Accepted 28 March 2000

Members of the integrin family of adhesion receptors mediate both cell-cell and cell-matrix interactions and have been shown to play vital roles in embryonic development, wound healing, metastasis, and other biological processes. The integrin alpha 9beta 1 is a receptor for the extracellular matrix proteins osteopontin and tenacsin C and the cell surface immunoglobulin vascular cell adhesion molecule-1. This receptor is widely expressed in smooth muscle, hepatocytes, and some epithelia. To examine the in vivo function of alpha 9beta 1, we have generated mice lacking expression of the alpha 9 subunit. Mice homozygous for a null mutation in the alpha 9 subunit gene appear normal at birth but develop respiratory failure and die between 6 and 12 days of age. The respiratory failure is caused by an accumulation of large volumes of pleural fluid which is rich in triglyceride, cholesterol, and lymphocytes. alpha 9-/- mice also develop edema and lymphocytic infiltration in the chest wall that appears to originate around lymphatics. alpha 9 protein is transiently expressed in the developing thoracic duct at embryonic day 14, but expression is rapidly lost during later stages of development. Our results suggest that the alpha 9 integrin is required for the normal development of the lymphatic system, including the thoracic duct, and that alpha 9 deficiency could be one cause of congenital chylothorax.

* Corresponding author. Mailing address: Lung Biology Center, UCSF Box 0854, San Francisco, CA 94143-0854. Phone: (415) 206-5901. Fax: (415) 206-4123. E-mail: deans{at}itsa.ucsf.edu.

Molecular and Cellular Biology, July 2000, p. 5208-5215, Vol. 20, No. 14
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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