| First Author | Ng L | Year | 2001 |
| Journal | Hum Mol Genet | Volume | 10 |
| Issue | 23 | Pages | 2701-8 |
| PubMed ID | 11726557 | Mgi Jnum | J:118402 |
| Mgi Id | MGI:3699539 | Doi | 10.1093/hmg/10.23.2701 |
| Citation | Ng L, et al. (2001) Suppression of the deafness and thyroid dysfunction in Thrb-null mice by an independent mutation in the Thra thyroid hormone receptor alpha gene. Hum Mol Genet 10(23):2701-8 |
| abstractText | Deletion of thyroid hormone receptor beta (TR beta), a ligand-dependent transcription factor encoded by the Thrb gene, causes deafness and thyroid hyperactivity in Thrb-null (Thrb(tm1/tm1)) mice and in a recessive form of the human syndrome of resistance to thyroid hormone. Here, we have determined that a targeted mutation (Thra(tm2)) in the related Thra gene, encoding thyroid hormone receptor alpha suppresses these phenotypes in mice. Thra encodes a TR alpha 1 receptor which is non-essential for hearing and a TR alpha 2 splice variant of unknown function that neither binds thyroid hormone nor transactivates. The Thra(tm2) mutation deletes TR alpha 2 and concomitantly causes overexpression of TR alpha 1 as a consequence of the exon structure of the gene. Thra(tm2/tm2) mice have normal auditory thresholds indicating that TR alpha 2 is dispensable for hearing, and have only marginally reduced thyroid activity. However, a potent function for the Thra(tm2) allele is revealed upon its introduction into Thrb(tm1/tm1) mice, where it suppresses the auditory and thyroid phenotypes caused by loss of TR beta. These findings reveal a novel modifying function for a Thra allele and suggest that increased expression of TR alpha 1 may substitute for the absence of TR beta. The TR isotypes generated by the distinct Thrb and Thra genes represent a small family of receptors that have diverged to mediate different physiological roles; however, the ability of changes in Thra expression to compensate for loss of Thrb indicates that many functions of these genes remain closely related. |
