|
|
The Iodine Group | |
|
Home | Orthoiodosupplementation | Body | Disease | Special | Overviews |
||
|
|
Everett
Localization and functional studies of pendrin in the mouse inner ear provide insight about the etiology of deafness in pendred syndrome.Royaux IE, Belyantseva IA, Wu T, Kachar B, Everett LA, Marcus DC, Green ED. J Assoc Res Otolaryngol. 2003 Sep;4(3):394-404. [abstract only]
"Immunolocalization studies of mouse cochlea and vestibular end-organ were performed to study the expression pattern of pendrin, the protein encoded by the Pendred syndrome gene (PDS), in the inner ear. The protein was restricted to the areas composed of specialized epithelial cells thought to play a key role in regulating the composition and resorption of endolymph. In the cochlea, pendrin was abundant in the apical membrane of cells in the spiral prominence and outer sulcus cells (along with their root processes). In the vestibular end-organ, pendrin was found in the transitional cells of the cristae ampullaris, utriculi, and sacculi as well as in the apical membrane of cells in the endolymphatic sac. Pds-knockout (Pds-/-) mice were found to lack pendrin immunoreactivity in all of these locations. Histological studies revealed that the stria vascularis in Pds-/- mice was only two-thirds the thickness seen in wild-type mice, with the strial marginal cells showing irregular shapes and sizes. Functional studies were also performed to examine the role of pendrin in endolymph homeostasis. Using double-barreled electrodes placed in both the cochlea and the utricle, the endocochlear potential and endolymph potassium concentration were measured in wild-type and Pds-/- mice. Consistent with the altered strial morphology, the endocochlear potential in Pds-/- mice was near zero and did not change during anoxia. On the other hand, the endolymphatic potassium concentration in Pds-/- mice was near normal in the cochlea and utricle. Together, these results suggest that pendrin serves a key role in the functioning of the basal and/or intermediate cells of the stria vascularis to maintain the endocochlear potential, but not in the potassium secretory function of the marginal cells."
Targeted disruption of mouse Pds provides insight about the inner-ear defects encountered in Pendred syndrome.Everett LA, Belyantseva IA, Noben-Trauth K, Cantos R, Chen A, Thakkar SI, Hoogstraten-Miller SL, Kachar B, Wu DK, Green ED. Hum Mol Genet. 2001 Jan 15;10(2):153-61. "Following the positional cloning of PDS, the gene mutated in the deafness/goitre disorder Pendred syndrome (PS), numerous studies have focused on defining the role of PDS in deafness and PS as well as elucidating the function of the PDS-encoded protein (pendrin). To facilitate these efforts and to provide a system for more detailed study of the inner-ear defects that occur in the absence of pendrin, we have generated a Pds-knockout mouse. Pds(-/-) mice are completely deaf and also display signs of vestibular dysfunction. The inner ears of these mice appear to develop normally until embryonic day 15, after which time severe endolymphatic dilatation occurs, reminiscent of that seen radiologically in deaf individuals with PDS mutations. Additionally, in the second postnatal week, severe degeneration of sensory cells and malformation of otoconia and otoconial membranes occur, as revealed by scanning electron and fluorescence confocal microscopy. The ultrastructural defects seen in the Pds(-/-) mice provide important clues about the mechanisms responsible for the inner-ear pathology associated with PDS mutations."
Expression pattern of the mouse ortholog of the Pendred's syndrome gene (Pds) suggests a key role for pendrin in the inner ear.Everett LA, Morsli H, Wu DK, Green ED. Proc Natl Acad Sci U S A. 1999 Aug 17;96(17):9727-32.
"Pendred's syndrome is an autosomal-recessive disorder characterized by deafness and goiter. After our recent identification of the human gene mutated in Pendred's syndrome (PDS), we sought to investigate in greater detail the expression of the gene and the function of its encoded protein (pendrin). Toward that end, we isolated the corresponding mouse ortholog (Pds) and performed RNA in situ hybridization on mouse inner ears (from 8 days postcoitum to postnatal day 5) to establish the expression pattern of Pds in the developing auditory and vestibular systems. Pds expression was detected throughout the endolymphatic duct and sac, in distinct areas of the utricle and saccule, and in the external sulcus region within the cochlea. This highly discrete expression pattern is unlike that of any other known gene and involves several regions thought to be important for endolymphatic fluid resorption in the inner ear, consistent with the putative functioning of pendrin as an anion transporter. These studies provide key first steps toward defining the precise role of pendrin in inner ear development and elucidating the pathogenic mechanism for the deafness seen in Pendred's syndrome."
Pendred syndrome is caused by mutations in a putative sulphate transporter gene (PDS).Everett LA, Glaser B, Beck JC, Idol JR, Buchs A, Heyman M, Adawi F, Hazani E, Nassir E, Baxevanis AD, Sheffield VC, Green ED. Nat Genet. 1997 Dec;17(4):411-22. [abstract only]
"Pendred syndrome is a
recessively inherited disorder with the hallmark features of
congenital deafness and thyroid goitre. By some estimates, the
disorder may account for upwards of 10% of hereditary deafness.
Previous genetic linkage studies localized the gene to a broad
interval on human chromosome 7q22-31.1. Using a positional cloning
strategy, we have identified the gene (PDS) mutated in Pendred
syndrome and found three apparently deleterious mutations, each
segregating with the disease in the respective families in which they
occur. PDS produces a transcript of approximately 5 kb that was found
to be expressed at significant levels only in the thyroid. The
predicted protein, pendrin, is closely related to a number of known
sulphate transporters. These studies provide compelling evidence that
defects in pendrin cause Pendred syndrome thereby launching a new area
of investigation into thyroid physiology, the pathogenesis of
congenital deafness and the role of altered sulphate transport in
human disease."
More articles by Everett, Green, and Royaux with Suzuki
|
|
Home | Orthoiodosupplementation | Body | Disease | Special Topics | OverviewsThe Iodine Group | Books | Disclaimers | Contact Us | Search
|
||
