Mutant gene-induced disorders of structure, function and thyroglobulin synthesis in congenital goitre (cog/cog) in mice.
We have investigated thyroid structure and function in mice homozygous for the chromosome 15 mutation, congenital goitre (cog). Abnormal thyroidal hypertrophy and reduced iodine uptake in cog/cog mice were observed as early as day 18 of gestation, corresponding to the onset of thyroid function. Growth continued unabated in mutants throughout the 10-month period of observation. By 2 months of age, thyroid cell hypertrophy obliterated nearly all follicular lumina in cog/cog glands and by 10 months mean mutant thyroid mass exceeded that of age-matched littermates. Twenty-fold serum concentrations of thyrotrophin were significantly increased at all ages examined. While wild type (+/+) and heterozygote (+/cog) mice are indistinguishable from each other, thyroids of homozygote mutants (cog/cog) and the +/cog type are easily discernible from thyroids of the +/+ type by microscopic and thyroglobulin (Tg) analyses. Thyrofollicular cells of both cog/cog and +/cog genotypes contain large vesicles of accumulated, nonglycosylated proteinaceous material not observed in cells from +/+ mice. Autoradiography showed 125I was incorporated only into Tg within recognizable follicular lumina of thyroids from +/cog mice. Serum concentrations of tri-iodothyronine are depressed during development in cog/cog mice. Serum concentrations of thyroxine are depressed during postnatal development but increase progressively to normal concentrations by 10 months of age. Our analyses indicate that full size Tg is produced in thyroid cells from cog/cog mice, though in a greatly reduced quantity, and that Tgs which are several sizes smaller than normal are also produced in both homozygote and heterozygote thyroids.(ABSTRACT TRUNCATED AT 250 WORDS)
Jackson Laboratory, Bar Harbor, Maine 04609.
L R
LR
Adkison
S
S
Taylor
W G
WG
Beamer
D000818:Animals; D005260:Female; D005333:Fetus; D006042:Goiter / Q000097:blood / Q000235:genetics* / Q000473:pathology; D006984:Hypertrophy; D007457:Iodine Radioisotopes / Q000378:metabolism; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D012313:RNA / Q000032:analysis; D013954:Thyroglobulin / Q000096:biosynthesis*; D013961:Thyroid Gland / Q000473:pathology*; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood; D013997:Time Factors; D014284:Triiodothyronine / Q000097:blood
D007457:Iodine Radioisotopes; D014284:Triiodothyronine; D012313:RNA; D013972:Thyrotropin; D013954:Thyroglobulin; D013974:Thyroxine