Fig. 5.

T3 recovers auditory sensitivity in Dio2^-/- mice. (A) Mean ABR thresholds ±SEM in mice at P28 after T3 treatment starting at P10, P16, or P23. Untreated groups are shown in columns marked -. T3 was given in drinking water (0.3 μg/ml) to nursing dams and weaned progeny. Compared to untreated mice, thresholds were substantially corrected in Dio2^-/- progeny when treatment started at P10 (P = 0.002), partly corrected when started at P16 (P = 0.005), and not significantly corrected when started at P23 (P = 0.06). Similar results were obtained for 8-, 16-, and 32-kHz stimuli. (B) Serum levels of total T3 and total T4 in P16 pups after T3 treatment (0.3 μg/ml) from P10. Treatment (+T3) increased T3 levels 2- to 5-fold over untreated levels (-T3). As expected, T3 treatment also suppressed the function of the pituitary–thyroid axis, thereby reducing T4 levels. Groups contained two pools of serum from 16–20 pups except for the T4 assays in +T3 groups, which contained single pools of serum from n = 5–8 pups. (C) The thresholds and definition of ABR waveforms were improved in Dio2^-/- mice when treated from P10, but were less improved when treated from P16 and not improved when treated from P23. Thresholds are underlined. Traces are shown on a 4-μV fixed scale. (D–G) Improved cochlear morphology in Dio2^-/- mice after T3 treatment from P10 until analysis at P16. In untreated Dio2^-/- pups (D), the TM is malformed and the inner sulcus epithelium (ISE) is thicker with taller, columnar cells than in untreated Dio2^+/- pups (F). T3 improved ISE differentiation and the shape of the TM in Dio2^-/- pups (E) but did not obviously alter morphology in Dio2^+/- control littermates (G). Inner and outer hair cells are marked by black and white filled arrowheads, respectively, in D. Sections show comparable apical turns of the cochlea. Groups, n = 3. (Scale bar: 50 μm for D–F.)