Absence of thyroid hormone receptor β-retinoid X receptor interactions in auditory function and in the pituitary-thyroid axis

THYROID hormone receptor beta-deficient (TR beta-/-) mice have defective auditory-evoked brain stem responses (ABR). Since in vitro, TR beta binds to DNA as homodimers or as heterodimers with retinoid X receptors (RXRs), we investigated whether the TR beta-/- phenotype may reflect loss of RXR-TR beta heterodimer or TR beta homodimer function. Normal ABR thresholds were recorded in RXR beta-/-, RXR gamma-/-, RXR alpha-/+ and RXR compound mutant mice. When RXR mutations were introduced onto TR beta-/+ or TR beta-/- backgrounds, thresholds were dictated solely by TR beta and not RXR genotype. TR beta-/- 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 TR beta may function in vivo by an RXR-independent mechanism in the auditory system and pituitary-thyroid axis. NeuroReport 9:2933-2937 (C) 1998 Lippincott Williams & Wilkins.