ISSN:1420-3030    

DOI:10.1159/000259223

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Mouse models have proved valuable tools in the analysis of human genetic disorders. The identification of the genes mutated in classical mouse mutants and the analysis of the phenotype of mutants following targeted gene disruption have provided some clarification of the development and functioning of the inner ear. A number of these genes also play a role in human deafness. Analysis of mutations in both human and mouse deafness genes has identified a number of distinct phenomena that contribute to the observed phenotype.

ISSN:1420-3030    

DOI:10.1159/000259224

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Retrovirus-mediated gene transfer holds great promise for elucidating key genes in the development and function of the inner ear. Retroviral vectors offer a number of advantages over other gene transfer methods including stable and efficient integration into the host genome, high levels of transcription and restriction of expression to a target area. Because of the wide variety of recombinant retroviral vectors currently available, this review outlines which vectors are appropriate for particular applications. Successful strategies for infecting the ear are reviewed and current drawbacks and future directions are discussed.

ISSN:1420-3030    

DOI:10.1159/000259226

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

This review describes the H2kbtsA58 transgenic mouse (Immortomouse) and its application to the production of conditionally immortalised cell lines from sensory epithelia within the mammalian inner ear. Established cell lines should overcome many of the technical difficulties associated with experimental procedures in auditory and vestibular research. These include the limited amount of tissue available and the relatively complex and laborious dissection. Conditional immortalisation should also allow essential studies on the molecular and cellular mechanisms that govern both the differentiation of sensory cells and the development of sensory epithelia.

ISSN:1420-3030    

DOI:10.1159/000259227

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

In order to understand the molecular events underlying differentiation and development in the inner ear, we need to identify and characterize the molecular ‘switches’ involved in the regulation of gene expression in the system. The most important molecular regulators are represented by a family of proteins generically called transcription factors. This article reviews our current knowledge of the expression of several transcription factors in the ear and their implications for both development and homeostasis in the auditory org

ISSN:1420-3030    

DOI:10.1159/000259228

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

The development of individual cells as hair cells and supporting cells is a key step during the embryonic formation of the auditory system. However, at present the factors that play a role in the commitment and differentiation of cells as hair cells and supporting cells have not been identified. Recent advances in molecular biological techniques have led to the identification of candidate genes that may be involved in hair cell and supporting cell development, however it has been difficult to determine the specific effects of these genes. The development of new methods for gene transfer into post-mitotic cells should provide powerful new techniques for examining the specific effects of candidate genes. Virally mediated vectors, such as adenovirus and herpes simplex virus, and non-virally mediated vectors, such as lipofectins and biolistics, have been shown to efficiently transfer candidate genes into many different cell types, including hair cells, supporting cells, and spiral ganglion neurons. In addition, studies in other developing systems have demonstrated that these techniques can be used to determine the effects of expression of candidate genes during the specification of individual cell phenotypes. These results suggest that these vectors can be used effectively to study the role of specific genes during the development of the auditory system.

ISSN:1420-3030    

DOI:10.1159/000259229

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

The sensory cells of the ear, the hair cells, are damaged by loud noise or certain types of drugs. In the bird cochlea, new hair cells are produced to replace those that are lost. Regeneration also occurs in the vestibular epithelia of birds, fish, and mammals but does not occur in the mammalian cochlea. In order to further our understanding of the regeneration process in the bird cochlea, we have begun to identify the genes that are involved. However, the small size of this organ has made it difficult to use traditional molecular biology methods to address these problems. Recently, many molecular techniques have been adapted for use with small amounts of tissue. Northern blot analysis, the ribonuclease protection assay, semiquantitative PCR and differential display of mRNA are all techniques that are being used to greatly improve our understanding of hair cell regeneration and may eventually provide the information necessary to induce regeneration in hearing-impaired humans.

ISSN:1420-3030    

DOI:10.1159/000259230

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Many genes encoding proteins which are expressed in the auditory periphery have been identified in the last years. With single-cell reverse transcription-polymerase chain reaction (RT-PCR), the molecular analysis of gene expression can be done on the single-cell level. Furthermore a single-cell RT-PCR experiment can be combined with the electrophysiological characterization of an individual cell. The combination of these two methods will lead to a better understanding of how functional properties of neurons are controlled by the expression of complex proteins.

ISSN:1420-3030    

DOI:10.1159/000259231

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Our present understanding of excitatory neurotransmission has expanded enormously in the last decade through the use of molecular biology. In the mammalian cochlea, the analysis of excitatory amino acid receptor expression by the reverse transcription-polymease chain reaction (RT-PCR), in situ hybridization and immunochemistry has provided considerable evidence for glutamate as the afferent neurtransmitter. Using these molecular techniques, the ionotropic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA), kainate, N-methyl-D-aspartic acid (NMDA) and delta receptor subunits and the metabotropic glutamate receptors have all been detected in the cochlea, in either the spiral ganglion neurons, the hair cells or both. Due to the utility ofthe techniques and the diversity of expressed neurotransmitter receptors, molecular biology will continue to provide important information for researchers ofthe auditory periphery

ISSN:1420-3030    

DOI:10.1159/000259232

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

The ability to identify the expression of the protein subunits which assemble to form ionotropic receptors for acetylcholine and extracellular adenosine 5’-triphosphate (ATP) in individual cells of the inner ear provides examples of the high resolution and exquisite sensitivity which molecular biology brings to the study of hearing and balance. The data from these studies provide both fine detail with respect to the classification of the elements involved and an overview of the sites of potential interaction of both extracellular and intracellular signalling pathways. The high sensitivity necessitates a molecular physiological approach when using these techniques so that these data on the site and extent of expression can be balanced against functional significance. With the demonstration of expression of the α9 subunit of the nicotinic acetylcholine receptor in cochlear outer hair cells, molecular biology has provided an explanation for the unusual cholinergic receptor pharmacology of the olivocochlear efferent innervation which has confounded investigators for decades. In addition, a role for extracellular ATP as a signalling molecule regulating electrochemical gradients and neurotransmission within the inner ear is supported by the extent of P2 receptor expression in this tissue, data which beg for intense functional stu

ISSN:1420-3030    

DOI:10.1159/000259233

出版商:S. Karger AG    

年代:1997

数据来源: Karger