Effect of tissue non-specific alkaline phosphatase in maintenance of structure of murine colon and stomach

The gastrointestinal tract of mammals secretes a phospholipid-rich membrane that is enriched in alkaline phosphatase (AP) and surfactant proteins (sur factant-like particle, SLP). The production of this particle is stimulated in the small intestine by fat feeding and in cultured cells in vitro by tra nsfection with intestinal alkaline phosphatase (IAP). To test whether tissu e non-specific alkaline phosphatase (TNAP) was a factor in stimulating surf actant-like particle production in stomach and colon (tissues expressing TN AP), mice lacking this enzyme were studied. Mice were harvested at 8 days o f life, when body weight of homozygous animals (TNAP -/-) was about half th at of congenic controls (TNAP +/+) or heterozygotes (TNAP +/-), but before seizures had begun. No difference in content of the major SLP protein (65 k Da) by Western blotting or immunocytochemistry was seen in stomach or colon of TNAP -/- vs. TNAP +/+ animals, but the content was only about half in t he IAP-expressing small bowel. Transmission electron microscopy of the TNAP -/- small bowel showed large dilated lysosomes and residual bodies. Colono cytes and gastric surface epithelial cells from the same animals showed mit ochondria containing homogeneous dense inclusions, consistent with neutral lipid. In the underweight homozygous animals, there was a decrease in the n euronal content of submucosal ganglia in the jejunum and ileum and of myent eric ganglia in the jejunum of TNAP -/- animals. These findings suggest tha t (1) TNAP is not important in maintaining surfactant-like particle content of tissues that express TNAP, (2) normal fat absorption is important in ma intaining SLP content in the small intestine, and (3) TNAP is important in the maintenance of some intestinal structures, and perhaps their function. (C) 2000 Wiley-Liss, Inc.