Targeting hearing genes in mice.
The rate of identification of genes for hearing has clearly outpaced the rate of determination of the functions of these genes' products. The use of transgenic and knock-out mouse models is a powerful approach to the elucidation of gene function in the ear. A large number of gene-targeted mice with auditory defects have recently been created and characterized, and nine independent mouse lines in which Cre recombinase activity begins to be expressed during early embryonic development of the ear or is specifically expressed in hair cells during postnatal development will be useful for ear-specific gene manipulation when combined with mouse lines that have loxP sites flanking the genes of interest. Existing gene-trapped embryonic stem (ES) cells and existing targeting constructs are readily available; new targeting constructs can easily be created by modifying bacterial artificial chromosomes and using them to directly transfect and screen ES cells; and N-ethyl-N-nitrosourea mutagenesis of ES cells can create point mutations in specific genes. To minimize variation in hearing phenotypes and avoid undesired hearing defects, mutant mice in the common gene-targeting background strains (129 and C57BL/6) should be transferred into congenic CBA/CaJ, a strain with "gold standard" normal hearing. Valuable mutant strains can be maintained, distributed, and cryopreserved in one of four NIH-sponsored Mutant Mouse Regional Resource Centers. Targeting hearing genes in mice will provide unprecedented opportunities for collaboration and new directions in the hearing research community.
Gao
Jiangang
J
Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105-2794, USA.
Wu
Xudong
X
Zuo
Jian
J
D000818:Animals; D001306:Auditory Pathways / Q000502:physiology*; D001923:Brain Chemistry / Q000235:genetics*; D006309:Hearing / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D016296:Mutagenesis