Developmental changes of cone opsin expression but not retinal morphology in the hypothyroid Pax8 knockout mouse.
OBJECTIVE
The effects of postnatal hypothyroidism on retinal development and spatial patterning of cone opsin expression were studied in Pax8-deficient mice. Pax8(-/-) mice are incapable of synthesizing thyroxine and serve as a model for congenital hypothyroidism.


METHODS
Pax8(-/-), Pax8(+/-), and Pax8(+/+) littermates were studied. Serum thyroid hormone levels, body weight, and eye size were measured. Retinal cell-type-specific antibodies were used on frozen sections to examine the postnatal development of the major retinal cell classes and of retinal structure. The expression of short-wavelength-sensitive (S) and middle-to-long-wavelength-sensitive (M) cone opsins was assessed with opsin antibodies on retinal sections and whole retinas. The pattern of S opsin mRNA was assessed by in situ hybridization.


RESULTS
In Pax8(-/-) mice, S opsin was upregulated in all cones, whereas M opsin was downregulated throughout the retina, the wild-type dorsoventral gradients of S and M opsin expression were absent. Otherwise, Pax8(-/-) mice showed no overt mutant phenotype in eye size, gross retinal anatomy, and the time-course of structural differentiation of retinal photoreceptors, horizontal cells, bipolars, amacrines, ganglion cells, and Müller glia cells.


CONCLUSIONS
Pax8(-/-) mice show a pattern of cone opsin expression that differs substantially from the wild-type pattern, but exhibit no apparent alterations in general retinal development. The finding that a postnatal decrease in serum thyroid hormone yields changes in postnatal cone opsin expression is consistent with a ligand-dependent role of thyroid hormone receptor beta2 in S opsin repression and M opsin activation.
Glaschke
Anika
A
Max Planck Institute for Brain Research, Frankfurt am Main, Germany.
Glösmann
Martin
M
Peichl
Leo
L
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001835:Body Weight; D055358:Cone Opsins / Q000378:metabolism*; D003409:Congenital Hypothyroidism / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors / Q000502:physiology*; D012160:Retina / Q000254:growth & development* / Q000378:metabolism; D017949:Retinal Cone Photoreceptor Cells / Q000378:metabolism*; D055351:Retinal Neurons / Q000166:cytology* / Q000378:metabolism; D037042:Thyroid Hormone Receptors beta / Q000378:metabolism; D013974:Thyroxine / Q000008:administration & dosage / Q000097:blood; D014284:Triiodothyronine / Q000097:blood
D015415:Biomarkers; D055358:Cone Opsins; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors; C499496:Pax8 protein, mouse; D037042:Thyroid Hormone Receptors beta; D014284:Triiodothyronine; D013974:Thyroxine