Absence of thyroid hormone receptor beta-retinoid X receptor interactions in auditory function and in the pituitary-thyroid axis.
THYROID hormone receptor beta-deficient (TRbeta-/-) mice have defective auditory-evoked brain stem responses (ABR). Since in vitro, TRbeta binds to DNA as homodimers or as heterodimers with retinoid X receptors (RXRs), we investigated whether the TRbeta-/- phenotype may reflect loss of RXR-TRbeta heterodimer or TRbeta homodimer function. Normal ABR thresholds were recorded in RXRbeta-/-, RXRgamma-/-, RXRalpha-/+ and RXR compound mutant mice. When RXR mutations were introduced onto TRbeta-/+ or TRbeta-/- backgrounds, thresholds were dictated solely by TRbeta and not RXR genotype. TRbeta-/-mice also over-produce thyroid hormones and thyroid stimulating hormone; however, levels of these hormones were unaltered by RXR mutations. This suggests that, contrary to in vitro models, RXRs may be dispensable and that TRbeta may function in vivo by an RXR-independent mechanism in the auditory system and pituitary-thyroid axis.
Barros
A C
AC
Department of Human Genetics, Mount Sinai School of Medicine, New York, NY 10029, USA.
Erway
L C
LC
Krezel
W
W
Curran
T
T
Kastner
P
P
Chambon
P
P
Forrest
D
D
D000161:Acoustic Stimulation; D000818:Animals; D001309:Auditory Threshold / Q000502:physiology; D001933:Brain Stem / Q000502:physiology; D004268:DNA-Binding Proteins; D005072:Evoked Potentials, Auditory / Q000502:physiology; D017353:Gene Deletion; D006309:Hearing / Q000502:physiology*; D006579:Heterozygote; D006720:Homozygote; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009687:Nuclear Proteins; D010902:Pituitary Gland / Q000502:physiology*; D018168:Receptors, Retinoic Acid / Q000378:metabolism*; D011988:Receptors, Thyroid Hormone / Q000378:metabolism*; D047488:Retinoid X Receptors; D013961:Thyroid Gland / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism*
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; D047488:Retinoid X Receptors; D014157:Transcription Factors