A novel pleckstrin homology-related gene family defined by Ipl/Tssc3, TDAG51, and Tih1: tissue-specific expression, chromosomal location, and parental imprinting

We previously described a gene, Ipi (Tssc3), that is expressed selectively from the maternal allele in placenta, yolk sac, and fetal liver and that ma ps within the imprinted domain of mouse distal Chromosome (Chr) 7/human Chr 11p15.5 (Hum Mol Genet 6, 2021, 1997). Ipl is similar to TDAG51, a gene th at is involved in FAS/CD95 expression. Here we describe another gene, Tihl (TDAG/Ipl homologue 1), with equivalent sequence similarity to Ipl. Structu ral prediction indicates that the products of these three genes share a cen tral motif resembling a pleckstrin-homology (PH) domain, and TIH1 protein h as weal; sequence similarity to the PH-domain protein SEC7/CYTOHESIN. Like Ipl, Tihl is a small gene with a single small intron. Tih1 maps to distal m ouse Chr 1 and human Chr 1q31, chromosomal regions that have not shown evid ence for imprinting and, in contrast to Ipl, Tih1 is expressed equally from both parental alleles. Ipl, Tih1, and TDAG51 have overlapping but distinct patterns of expression. Tih1 and TDAG51 are expressed in multiple fetal an d adult tissues. In contrast, during early mouse development Ipl mRNA and p rotein are highly specific for two tissues involved in maternal/fetal excha nge: visceral endoderm of the yolk sac and labyrinthine trophoblast of the placenta. These findings highlight the dominance of chromosomal contest ove r gene structure in some examples of parental imprinting and extend previou s evidence for placenta-specific expression of imprinted genes. The data al so define a new subfamily of PH domain genes.