Strategy to introduce TM lacking the cytoplasmic domain into ES cells via homologous recombination. The wild-type allele for the TM gene, which is intronless, encodes a lectin-like domain (LLD), 6 epidermal growth-factor like repeats (EGF), a serine-threonine rich region (STR), a single transmembrane domain (TM), and a cytoplasmic tail (CT). DNA probes used for Southern blotting are shown. After homologous recombination of the targeting vector, the targeted ES cells were exposed to cre-recombinase for excision of theneo-TK genes.