Analysis of nuclear receptor function in the mouse auditory system.
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Animals↗
Biomedical subjects
Iwan Jones
Publications and source records attributed to Iwan Jones.
An emilin family extracellular matrix protein identified in the cochlear basilar membrane.
The precise movement of the cochlear basilar membrane (BM) stimulates the sensory hair cells during auditory transduction. However, the molecular composition of the BM that confers its specialized properties of support and elasticity is poorly understood. A differential screen of cochlear RNA from deaf mice lacking thyroid hormone receptor beta was used to identify a sequence encoding a secreted protein, which is abundant in the BM and is expressed at low levels in the heart, lung, and brain. The protein possesses several domains for protein interactions and is related to emilin (elastin microfibril interface-located protein) previously isolated from aorta. This cochlear emilin-2 mRNA is expressed in the tympanic border cells underlying the BM and an antibody detected protein in the extracellular matrix surrounding the collagenous fibers in the BM. These results identify emilin-2 as a major BM component and suggest that it contributes to the developmental assembly or function of the BM.
Amino Acid Sequence↗
The thyroid hormone receptor beta gene: structure and functions in the brain and sensory systems.
Thyroid hormone profoundly influences the development of the vertebrate nervous system. The thyroid hormone receptor beta gene (Thrb) is a key mediator of many of these actions. The Thrb gene is complex, spanning up to 400 kb in mammals, and differentially expresses distinct receptor subtypes through independent tissue-specific promoters and alternative splicing. These receptors serve a range of functions in the brain as well as particularly sensitive functions in the auditory and visual sensory systems. The Thrb gene illustrates how versatility in neurodevelopmental control can be achieved at the receptor level.
Animals↗
Molecular cloning and expression of thyroid hormone receptor alpha during salmonid development.
Thyroid hormones have been implicated as important regulators of teleost development. To gain a better understanding of the potential roles of the thyroid system in salmonids a genomic clone which encoded rainbow trout TR-alpha was isolated. This clone exhibited highest amino acid identity to Japanese flounder TR-alphaB (94%) and zebrafish TR-alpha1 (94%). Oligonucleotides were designed against the rainbow trout sequence and the complete coding region of Atlantic salmon TR-alpha was isolated by RACE-PCR. The Atlantic salmon sequence exhibited highest amino acid identity to rainbow trout TR-alpha (98%), Japanese flounder TR-alphaB (93%), and zebrafish TR-alpha1 (90%). Atlantic salmon TR-alpha exhibited the classic modular structure associated with members of the nuclear receptor superfamily and consisted of a divergent A/B domain while the DNA and ligand-binding domains were highly conserved to other teleost TR proteins. Temporal expression from the rainbow trout TR-alpha gene was monitored by semiquantitative RT-PCR at selected stages during rainbow trout embryonic and larval development. High levels of maternal transcripts were present at cleavage (Stage 6) which were rapidly degraded by gastrulation (Stage 13). Low levels of TR-alpha expression were then detected during organogenesis (Stages 20, 24, 26, 29, and 31). A peak in mRNA levels was observed at hatch (Stage 32) after which levels rose in a gradual manner during larval development (Stages 33, 34, 35, and 36) to reach maximal values at first feeding (Stage 37). These results suggest that the thyroid axis is functional and that embryonic and larval rainbow trout are at least capable of responding to thyroid hormones. These observations implicate the thyroid system as being an important regulator of salmonid development.
Amino Acid Sequence↗
Expression and regulation of fushi tarazu factor-1 and steroidogenic genes during reproduction in Arctic char (Salvelinus alpinus).
Teleost fushi tarazu factor-1 (FTZ-F1) is a potential regulator of steroidogenesis. The present study shows sex-specific regulation of Arctic char fushi tarazu factor-1 (acFF1) and steroidogenic genes during reproductive maturation and in response to hormone treatment. A link between gonadal expression of acFF1, steroidogenic acute regulatory protein (StAR), and cytochrome P450-11A (CYP11A), was observed in the reproductive maturation process, as elevated acFF1 mRNA and protein levels preceded increased StAR and CYP11A transcription. Sex-specific differences were observed as estrogen treatment resulted in down-regulated levels of acFF1 mRNA in testis and male head kidney, whereas no significant effect was observed in females. 11-Ketotestosterone (11-KT) down-regulated CYP11A and 3beta-hydroxysteroid dehydrogenase (3betaHSD) in head kidney and up-regulated CYP11A in testis. StAR remained unaffected by hormone treatment. This suggests that acFF1 is controlled by 17beta-estradiol, whereas the effects on CYP11A and 3betaHSD are mediated by 11-KT. Coexpression of acFF1, StAR, and CYP11A was observed in head kidney, in addition to gonads, indicating correlation between these steroidogenic genes. StAR and acFF1 were also coexpressed in liver, suggesting a potential role in cholesterol metabolism. Although these results indicate conserved steroidogenic functions for FTZ-F1 among vertebrates, they also raise the question of additional roles for FTZ-F1 in teleosts.
3-Hydroxysteroid Dehydrogenases↗