title: Developmental changes of cone opsin expression but not retinal morphology in the hypothyroid Pax8 knockout mouse.
abstract: 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.
authors.affiliation: Max Planck Institute for Brain Research, Frankfurt am Main, Germany.
authors.forename: Anika
authors.initials: A
authors.lastname: Glaschke
authors.forename: Martin
authors.initials: M
authors.lastname: Glösmann
authors.forename: Leo
authors.initials: L
authors.lastname: Peichl
mesh_terms: 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
chemical_list: 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