Retinoid-related receptor (ROR) alpha mRNA expression is altered in the brain of male mice lacking all ligand-binding thyroid hormone receptor (TR) isoforms.
In the vertebrate brain, the thalamus serves as a relay and integration station for diverse neuronal information en route from the periphery to the cortex. Deficiency of TH during development results in severe cerebral abnormalities similar to those seen in the mouse when the retinoic acid receptor (ROR)alpha gene is disrupted. To investigate the effect of the thyroid hormone receptors (TRs) on RORalpha gene expression, we used intact male mice, in which the genes encoding the alpha and beta TRs have been deleted. In situ hybridization for RORalpha mRNA revealed that this gene is expressed in specific areas of the brain including the thalamus, pons, cerebellum, cortex, and hippocampus. Our quantitative data showed differences in RORalpha mRNA expression in different subthalamic nuclei between wild-type and knock-out mice. For example, the centromedial nucleus of the thalamus, which plays a role in mediating nociceptive and visceral information from the brainstem to the basal ganglia and cortical regions, has less expression of RORalpha mRNA in the knockout mice (-37%) compared to the wild-type controls. Also, in the dorsal geniculate (+72%) and lateral posterior nuclei (+58%) we found more RORalpha mRNA in dKO as compared to dWT animals. Such differences in RORalpha mRNA expression may play a role in the behavioral alterations resulting from congenital hypothyroidism.
Vasudevan
Nandini
N
Laboratory of Neurobiology and Behavior, The Rockefeller University, 1230, York Ave, New York, NY 10021, USA. nuv1@psu.edu
Kia
Hosein Kami
HK
Hadjimarkou
Maria
M
Koibuchi
Noriyuki
N
Chin
William W
WW
Forrest
Douglas
D
Vennstrom
Bjorn
B
Pfaff
Donald
D
D000818:Animals; D001921:Brain / Q000378:metabolism*; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis / Q000235:genetics*; D037021:Thyroid Hormone Receptors alpha / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000096:biosynthesis / Q000235:genetics*
D057094:Nuclear Receptor Subfamily 1, Group F, Member 1; D020033:Protein Isoforms; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D037021:Thyroid Hormone Receptors alpha; D015534:Trans-Activators