Characterization of the mouse Tdgf1 gene and Tdgf pseudogenes.

Cripto protein is a member of the "EGF family" of growth factors present in colon tumors and in human and mouse undifferentiated teratocarcinoma cells. During gastrulation in the mouse, cripto-encoding transcripts are expressed in the forming mesoderm and later in the truncus arteriosus of the developing heart. As a necessary step prior to investigating the in vivo role of cripto through gene disruption, we have isolated all the genomic cripto-related sequences in the mouse. One gene (Tdgf1) and two pseudogenes (Tdgf2 and Tdgf3) have been isolated and characterized. The mouse Tdgf1 (coding for cripto), like the human gene, is divided into six exons. Comparison of the human and mouse genomic sequences reveals that mouse exons 1 and 3 are shorter than the corresponding human exons. The pseudogene Tdgf2 corresponds to about 1 kb of the mRNA and contains five base substitutions in the coding region that represent both silent and replacement substitutions. The pseudogene Tdgf3 corresponds only to the coding portion of Tdgf. Many mutations have been introduced in this pseudogene, suggesting its early origin. Alignments of the Tdgf3, human and mouse mRNA sequences, shows that this pseudogene has retained the 33 nucleotides of the human exon 3 that are missed in the Tdgf1 gene. Taken together, these data suggest that Tdgf3 is derived from an ancestral gene and that the human and mouse genes are probably evolving separately.