Introduction Alkaline phosphatases (APs, E.C.3.1.3.1., orthophosphoric monoester phosphohydrolases) are ubiquitous enzymes capable of hydrolyzing a wide variety of monophosphate esters at alkaline pH

Alkaline phosphatases (APs, E.C.3.1.3.1., orthophosphoric monoester phosphohydrolases) are ubiquitous enzymes capable of hydrolyzing a wide variety of monophosphate esters at alkaline pH optima. These enzymes exist in nature in species as different as E. coli and man, suggesting that APs have fundamental biological roles (for review see McComb et al., 1979). The in vivo function(s) of APs, however, have not been resolved and the physiological substrates have not been identified. APs are membrane-bound glycoproteins encoded by a multigene family composed of four loci in humans and three active loci in the mouse. The isozymes can be distinguished by their thermostability, inhibition kinetics, electrophoretic mobilities and immunoreactivity (for review see Harris, 1989). The tissue non-specific AP (TNAP) is expressed in a wide variety of tissues, including bone, liver, kidney, early placenta, etc. The enzyme is heat-labile and its activity inhibited uncompetitively by Lhomoarginine (Fishman and Sie, 1971). Three human and two mouse APs are designated tissue-specific (TSAPs) and show a highly restricted pattern of expression. The human intestinal AP (IAP) and placental AP (PLAP) are primarily expressed in the tissues that confer their name (McComb et al., 1979) and the germ cell AP (GCAP) isozyme is expressed in the testis (Chang et al., 1980), primordial germ cells (Hustin et al., 1987) and also in trace amounts in the thymus (Goldstein et al., 1982). The TSAP isozymes are more heat-stable, resisting temperatures of up to 70°C as in the case of PLAP and GCAP, and are inhibited uncompetitively by L-phenylalanine (Fishman and Sie, 1971). PLAP and GCAP are often overexpressed in cancer (Fishman et al., 1976), particularly ovarian serous cystadenocarcinoma (Vergote et al., 1987; Nozawa et al., 1989) and testicular seminoma (Lange et al., 1982; Jeppsson et al., 1983), where they serve as useful follow-up markers. We have recently cloned three TSAP genes from the mouse genome, i.e., embryonic AP (EAP), intestinal AP (IAP) and a putative pseudogene, using the human PLAP cDNA as a probe (Manes et al., 1990). Reverse-transcriptase polymerase chain reaction amplification of RNA revealed that the EAP gene is expressed in the two-cell to 159 Development 116, 159-165 (1992) Printed in Great Britain © The Company of Biologists Limited 1992