Two abnormal thyroglobulin-like polypeptides are produced from Afrikander cattle congenital goiter mRNA

In vitro translation of the mRNA from the congenital goiter tissue of Afrikander cattle directs the synthesis of two (Mr congruent to 250,000 and congruent to 75,000, respectively) abnormal thyroglobulin-like polypeptides. Common features of these polypeptides are the following: 1) both are immunoprecipitated by purified, anti-thyroglobulin antibody; 2) the signal sequence is present on their nascent polypeptide chains, and 3) their synthesis is apparently directed by the same high molecular weight mRNA. However, the goiter thyroglobulin mRNA shows, by Northern blot analysis, a slightly reduced size (congruent to 30 S) as compared to the mRNA from normal, bovine, thyroid tissue (33 S). Furthermore, a 10- to 15-fold decrease (as assessed by dot blot hybridization) in relative mRNA concentration was observed. Thus, it can be concluded that the genetic defect in congenital goiter of Afrikander cattle results in the synthesis of an altered mRNA which is present in decreased amount and directs the synthesis of two abnormal thyroglobulin-like polypeptides.