Thyroid hormone action is required for normal cone opsin expression during mouse retinal development.
OBJECTIVE
The expression of S- and M-opsins in the murine retina is altered in different transgenic mouse models with mutations in the thyroid hormone receptor (TR)-beta gene, demonstrating an important role of thyroid hormone (TH) in retinal development.


METHODS
The spatial expression of S- and M-opsin was compared in congenital hypothyroidism and in two different TR mutant mouse models. One mouse model contains a ligand-binding mutation that abolishes TH binding and results in constitutive binding to nuclear corepressors. The second model contains a mutation that blocks binding of coactivators to the AF-2 domain without affecting TH binding.


RESULTS
Hypothyroid newborn mice showed an increase in S-opsin expression that was completely independent of the genotype. Concerning M-opsin expression, hypothyroidism caused a significant decrease (P < 0.01) only in wild-type animals. When TRbeta1 and -beta2 were T3-binding defective, the pattern of opsin expression was similar to TRbeta ablation, showing increased S-opsin expression in the dorsal retina and no expression of M-opsin in the entire retina. In an unexpected finding, immunostaining for both opsins was detected when both subtypes of TRbeta were mutated in the helix 12 AF-2 domain.


CONCLUSIONS
The results show, for the first time, that the expression of S- and M-opsin is dependent on normal thyroid hormone levels during development.
Pessôa
Cristiano N
CN
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, CCS, Cidade Universitária, Ilha do Fundão, Rio de Janeiro, Brazil.
Santiago
Leticia A
LA
Santiago
Diana A
DA
Machado
Danielle S
DS
Rocha
Fernando A F
FA
Ventura
Dora F
DF
Hokoç
Jan Nora
JN
Pazos-Moura
Carmen C
CC
Wondisford
Fredric E
FE
Gardino
Patricia F
PF
Ortiga-Carvalho
Tania M
TM
D000818:Animals; D000831:Animals, Newborn; D002452:Cell Count; D003409:Congenital Hypothyroidism / Q000378:metabolism*; D004195:Disease Models, Animal; D004596:Electroretinography; D005260:Female; D007124:Immunoenzyme Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation; D012160:Retina / Q000254:growth & development* / Q000378:metabolism; D017949:Retinal Cone Photoreceptor Cells / Q000378:metabolism*; D017299:Rod Opsins / Q000378:metabolism*; D037042:Thyroid Hormone Receptors beta / Q000235:genetics; D013963:Thyroid Hormones / Q000502:physiology*
D017299:Rod Opsins; D037042:Thyroid Hormone Receptors beta; D013963:Thyroid Hormones; C095854:middle-wavelength opsin; C095853:short-wavelength opsin