Retarded developmental expression and patterning of retinal cone opsins in hypothyroid mice.
Color vision is mediated by cone photoreceptors that express opsin photopigments with sensitivities to different light wavelengths. Most mammals, including mice, differentially express M and S opsins for response to medium-long and short wavelengths, respectively. Previous studies demonstrated that a thyroid hormone receptor (TRbeta2) is critical for opsin patterning: in TRbeta2-deficient mice, M opsin is lost and all cones instead express S opsin. Here, to investigate the requirement for thyroid hormone in cone development, we studied Tshr(-/-)mice as a model of congenital hypothyroidism. The onset of M opsin expression in Tshr(-/-)mice was severely delayed until after postnatal d 17 (P17), and M opsin expression failed to attain normal levels at older adult ages. S opsin showed a subtler change with an extended distribution pattern over the superior-inferior axis of the retina. Similar opsin abnormalities were detected in wild-type C57BL/6J mice made hypothyroid by methimazole treatment. In Tshr(-/-) mice, T(3) treatment from P8 recovered significant M opsin expression at P17. Tshr(-/-) mice produced normal numbers of cones, indicating that the major requirement for thyroid hormone is in opsin patterning rather than in cone generation. The phenotype is similar to, although milder than, that caused by loss of TRbeta2 and indicates the necessity for thyroid hormone for cone maturation.
Lu
Ailing
A
National Institute of Diabetes and Digestive and Kidney Diseases, Clinical Endocrinology Branch, National Institutes of Health, Bethesda, Maryland 20892-1772, USA.
Ng
Lily
L
Ma
Michelle
M
Kefas
Benjamin
B
Davies
Terry F
TF
Hernandez
Arturo
A
Chan
Chi-Chao
CC
Forrest
Douglas
D
D000818:Animals; D019521:Body Patterning / Q000187:drug effects / Q000235:genetics*; D055358:Cone Opsins / Q000235:genetics* / Q000378:metabolism; D003409:Congenital Hypothyroidism / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D008713:Methimazole; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008954:Models, Biological; D011247:Pregnancy; D011989:Receptors, Thyrotropin / Q000235:genetics; D012160:Retina / Q000187:drug effects / Q000473:pathology; D017949:Retinal Cone Photoreceptor Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors; D014284:Triiodothyronine / Q000494:pharmacology
D055358:Cone Opsins; D011989:Receptors, Thyrotropin; D014284:Triiodothyronine; D008713:Methimazole