Mapping of the α-Tectorin Gene (TECTA) to Mouse Chromosome 9 and Human Chromosome 11: A Candidate for Human Autosomal Dominant Nonsyndromic Deafness

doi:10.1006/geno.1997.5159

Genomics

Volume 48, Issue 1, 15 February 1998, Pages 46-51

https://doi.org/10.1006/geno.1997.5159 Get rights and content

Abstract

α-Tectorin is one of the major noncollagenous components of the mammalian tectorial membrane in the inner ear. We have mapped the gene encoding α-tectorin to mouse chromosome 9 and human chromosome 11 in a known region of conserved synteny. Human YAC clones containing α-tectorin have been identified, demonstrating physical linkage to the anonymous markerD11S925.This places α-tectorin within the genetic interval that contains both the human nonsyndromic autosomal dominant deafness DFNA12 and the proximal limit of a subset of deletions within Jacobsen syndrome. Thus both DFNA12 and the hearing loss in some cases of Jacobsen syndrome may be due to haploinsufficiency forTECTA.

References (28)

M. Breen et al.
Towards high-resolution maps of the mouse and human genomes—A facility for ordering markers to 0.1 cM resolution
Hum. Mol. Genet.
(1994)
M. Davis et al.
Refinement of two chromosome 11q regions of loss of heterozygosity in ovarian cancer
Cancer Res.
(1996)
R.W. Debry et al.
Human/mouse homology relationships
Genomics
(1996)
W.F. Dietrich et al.
A comprehensive genetic map of the mouse genome
Nature
(1996)
H. Gabra et al.
Definition and refinement of a region of loss of heterozygosity at 11q23.3–q24.3 in epithelial ovarian cancer associated with poor prognosis
Cancer Res.
(1996)
T. Hudson et al.
An STS-based map of the human genome
Science
(1995)
D.C. Hughes
Paradigms and paradoxes: Mouse (and human) models of genetic deafness
Audiol. Neurootol.
(1997)
P. Jacobsen et al.
An (11;21) translocation in four generations with chromosome 11 abnormalities in the offspring
Hum. Hered.
(1973)
C. Jones et al.
Physical linkage of the fragile site FRA11B and a Jacobsen syndrome chromosome deletion breakpoint in 11q23.3
Hum. Mol. Genet.
(1994)
C. Jones et al.
Association of a chromosome deletion syndrome with a fragile site within the proto-oncogene
CBL2. Nature
(1995)

R. Kalluri et al.

Isoform switching of Type IV collagen is developmentally arrested in X-linked Alport syndrome leading to increased susceptibility of renal basement membranes to endoproteolysis

J. Clin. Invest.

(1997)

D.P. Kelsell et al.

Development of a panel of monochromosomal somatic-cell hybrids for rapid gene mapping

Ann. Hum. Genet.

(1995)

R. Killick et al.

Molecular cloning of chick β-tectorin, an extracellular matrix molecule of the inner ear

J. Cell Biol.

(1995)

Cited by (33)

Clinical aspects of an autosomal dominantly inherited hearing impairment linked to the DFNA60 locus on chromosome 2q23.1-2q23.3
2013, Hearing Research
Citation Excerpt :
Two genes are known to be associated with mid-frequency hearing impairment: TECTA and COL11A2. Mutations in these genes cause alterations in the tectorial membrane (Hughes et al., 1998; McGuirt et al., 1999). The TECTA gene encodes α-tectorin, a major non-collagenous component of the tectorial membrane in the cochlea (Legan and Richardson, 1997).
A total of 64 loci for autosomal dominant non-syndromic hearing impairment have been described, and the causative genes have been identified for 24 of these. The present study reports on the clinical characteristics of an autosomal dominantly inherited hearing impairment that is linked to a region within the DFNA60 locus located on chromosome 2 in q22.1–24.1.
A pedigree spanning four generations was established with 13 affected individuals. Linkage analysis demonstrated that the locus extended over a 2.96 Mb region flanked by markers D2S2335 and D2S2275. The audiograms mainly showed a distinctive U-shaped configuration. Deterioration of hearing started at a wide age range, from 12 to 40 years. Cross-sectional analysis showed rapid progression of hearing impairment from mild to severe, between the ages of 40 and 60 years, a phenomenon that is also observed in DFNA9 patients. The results of the individual longitudinal analyses were generally in line with those obtained by the cross-sectional analysis. Speech recognition scores related to the level of hearing impairment (PTA_1,2,4 kHz) appeared to be fairly similar to those of presbyacusis patients. It is speculated that hearing impairment starting in mid-life, as shown by DFNA60 patients, could play a role in the development of presbyacusis. Furthermore, speech recognition did not deteriorate appreciably before the sixth decade of life. We conclude that DFNA60 should be considered in hearing impaired patients who undergo a rapid progression in middle age and are negative for DFNA9. Furthermore, cochlear implantation resulted in good rehabilitation in two DFNA60 patients.
Effectors of tridimensional cell morphogenesis and their evolution
2012, Seminars in Cell and Developmental Biology
Citation Excerpt :
Targeted inactivation of β-tectorin in mice disrupts the TM matrix and thus impairs sound transmission [62]. Mutations in α-tectorin provoke human deafness [63,64], including dominant hearing loss due to a punctual mutation (Y1870C) in the ZPD [64]. Strikingly, engineering a corresponding mutation in α-tectorin in mice [65], or even in the Drosophila protein Miniature [31], leads to dominant defects in hearing or epidermal morphogenesis, respectively.
One of the most challenging problems in biology resides in unraveling the molecular mechanisms, hardwired in the genome, that define and regulate the multiscale tridimensional organization of organs, tissues and individual cells. While works in cultured cells have revealed the importance of cytoskeletal networks for cell architecture, in vivo models are now required to explore how such a variety in cell shape is produced during development, in interaction with neighboring cells and tissues. The genetic analysis of epidermis development in Drosophila has provided an unbiased way to identify mechanisms remodeling the shape of epidermal cells, to form apical trichomes during terminal differentiation. Since hearing in vertebrates relies on apical cell extensions in sensory cells of the cochlea, called stereocilia, the mapping of human genes causing hereditary deafness has independently identified several factors required for this peculiar tridimensional organization. In this review, we summarized recent results obtained toward the identification of genes involved in these localized changes in cell shape and discuss their evolution throughout developmental processes and species.
Gene Expression Profile of the Mouse Organ of Corti at the Onset of Hearing
2004, Genomics
Citation Excerpt :
Tectorins are extracellular matrix proteins primarily found in surrounding tissues of the inner ear sensory epithelia [11] and they are essential components of the tectorial and otoconial membranes [12]. Mutations in TECTA have been associated with several deafness syndromes [13–19]. Additional highly expressed extracellular matrix proteins include several types of collagen.
We describe the generation of an expressed sequence tag (EST) database of the mouse organ of Corti (OC). Over 20,000 independent clones were isolated, analyzed, and grouped into 8690 unique gene clusters. A large pool of novel genes unique to the OC was identified. Sequence alignments frequently revealed alternatively spliced forms of known genes potentially relevant in the OC function. We have also electronically mapped a subset of OC mouse ESTs to several syntenic regions associated with human autosomal and recessive deafness, which may prove useful for the identification of new positional candidates for these human diseases. The EST dataset is available as an interactive Web-based public database at http://neibank.nei.nih.gov. This resource provides both a view of the profile of gene expression in the OC at the onset of hearing and a tool to identify novel genes of importance in hearing.
Structure and innervation of the cochlea
2003, Brain Research Bulletin
The role of the cochlea is to transduce complex sound waves into electrical neural activity in the auditory nerve. Hair cells of the organ of Corti are the sensory cells of hearing. The inner hair cells perform the transduction and initiate the depolarization of the spiral ganglion neurons. The outer hair cells are accessory sensory cells that enhance the sensitivity and selectivity of the cochlea. Neural feedback loops that bring efferent signals to the outer hair cells assist in sharpening and amplifying the signals. The stria vascularis generates the endocochlear potential and maintains the ionic composition of the endolymph, the fluid in which the apical surface of the hair cells is bathed. The mechanical characteristics of the basilar membrane and its related structures further enhance the frequency selectivity of the auditory transduction mechanism. The tectorial membrane is an extracellular matrix, which provides mass loading on top of the organ of Corti, facilitating deflection of the stereocilia. This review deals with the structure of the normal mature mammalian cochlea and includes recent data on the molecular organization of the main cell types within the cochlea.
Thyroid hormone-deficient period prior to the onset of hearing is associated with reduced levels of β-tectorin protein in the tectorial membrane: Implication for hearing loss
2001, Journal of Biological Chemistry
Citation Excerpt :
The major non-collagenous proteins of the mammalian tectorial membrane, α- and β-tectorins, have been identified as the products of two single genes (12). The α-tectorin gene maps to mouse chromosome 9 and human chromosome 11q22–29 (29), and β-tectorin maps to mouse chromosome 19, in a region that shows synteny with human 10q25–26 (30). α-Tectorin comprises an NH2-terminal region with similarity to the globular G0 domain of entactin, a large central region with three full and two partial repeats homologous to the D domain of prepro-von Willebrand factor and a C-terminal zona pellucida domain (12).
The genes for α- and β-tectorin encode the major non-collagenous proteins of the tectorial membrane. Recently, a targeted deletion of the mouse α-tectorin gene was found to cause loss of cochlear sensitivity (1). Here we describe that mRNA levels for β-tectorin, but not α-tectorin, are significantly reduced in the cochlear epithelium under constant hypothyroid conditions and that levels of β-tectorin protein in the tectorial membrane are lower. A delay in the onset of thyroid hormone supply prior to onset of hearing, recently described to result in permanent hearing defects and loss of active cochlear mechanics (2), can also lead to permanently reduced β-tectorin protein levels in the tectorial membrane. β-Tectorin protein levels remain low in the tectorial membrane up to one year after the onset of thyroid hormone supply has been delayed until postnatal day 8 or later and are associated with an abnormally structured tectorial membrane and the loss of active cochlear function. These data indicate that a simple delay in thyroid hormone supply during a critical period of development can lead to low β-tectorin levels in the tectorial membrane and suggest for the first time that β-tectorin may be required for development of normal hearing.
Identification of a novel frameshift mutation in the tecta gene in an iranian family with autosomal nonsyndromic hearing loss
2021, Acta Medica Iranica

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^☆: Mapping data from this article have been deposited with the Mouse Genome Database under Accession No. MGD-JNUM-43211 and with the Genome Data Base under Accession No. 9255418.

¹: To whom correspondence should be addressed at MRC Institute of Hearing Research, University Park, University of Nottingham, Nottingham NG7 2RD, UK. Telephone: (115) 922 3431. Fax: (115) 951 8503. E-mail:[email protected].

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Regular ArticleMapping of the α-Tectorin Gene (TECTA) to Mouse Chromosome 9 and Human Chromosome 11: A Candidate for Human Autosomal Dominant Nonsyndromic Deafness☆

Abstract

Towards high-resolution maps of the mouse and human genomes—A facility for ordering markers to 0.1 cM resolution

Hum. Mol. Genet.

Refinement of two chromosome 11q regions of loss of heterozygosity in ovarian cancer

Cancer Res.

Human/mouse homology relationships

Genomics

A comprehensive genetic map of the mouse genome

Nature

Definition and refinement of a region of loss of heterozygosity at 11q23.3–q24.3 in epithelial ovarian cancer associated with poor prognosis

Cancer Res.

An STS-based map of the human genome

Science

Paradigms and paradoxes: Mouse (and human) models of genetic deafness

Audiol. Neurootol.

An (11;21) translocation in four generations with chromosome 11 abnormalities in the offspring

Hum. Hered.

Physical linkage of the fragile site FRA11B and a Jacobsen syndrome chromosome deletion breakpoint in 11q23.3