The congenital goiter mutation is linked to the thyroglobulin gene in the mouse

Rat thyroglobulin (TG) cDNA clones were used to identify DNA restriction fragment variants among inbred mouse strains. One of these variants was shown to be closely linked to the recessive mutation congenital goiter (cog), which had previously been mapped to mouse chromosome 15. These results indicate that the structural gene for thyroglobulin is on chromosome 15 and suggest that a mutation at the site of the TG gene is the basis of the cog defect. No differences were observed between cog/cog and +/+ DNA in Southern blots using TG cDNA probes corresponding to 88% of the coding sequences, suggesting that the cog mutation is not due to a large deletion of this portion of the gene. Neither was there any obvious qualitative or quantitative difference between mutant and normal TG mRNA as judged by blot hybridization of electrophoretically fractionated thyroid RNAs. The thyroglobulin gene locus (Tgn) was mapped near the glutamic-pyruvic transaminase isoenzyme locus Gpt-1. The Tgn locus is syntenic with the c-myc protooncogene locus (Myc) in the mouse as in the rat and man.