Tg cDNA sequence of cog/cog mice with congenital hypothyroid goiter differs by one nucleotide from that of euthyroid AKR/J mice. The complete cog Tg coding sequence and the primary structure of the deduced cog Tg protein are shown. The preparation of thyroid cDNA libraries from the two isogenic strains of mice, library screening, and DNA sequencing of selected clones, is described in Materials and Methods. The deduced cog Tg protein sequence differs in six locations from that recently reported in GenBank (accession no. U76389) for normal outbred mice (the differing codons are shown as underlined areas). Of these differences, only the nucleotide substitution (CTC to CCC) at position 6848, resulting in a Leu-2263 → Pro mutation which resides in the acetylcholinesterase-homology domain of Tg, differs between the Tg sequences of cog/cog and AKR/J mice.