International Mammalian Genome Society

The 15th International Mouse Genome Conference (2001)

Table of Contents * Complex Genetics * Developmental Genetics * Gene Annotation * Gene Discovery * Genome Sequencing * Functional Genomics * Mutagenesis * Presentations * Verne Chapman Memorial Lecture

Dr. Jiewu Yang
MRC Harwell
MRC Mammalian Genetics Unit and UK Mouse Genome Centre
Harwell
Didcot
OX11 0RD
UK

Co-Authors: 1) Hardisty RE, 1) Varela A., 1) Mburu P., 1) Pritchard C, 1)Tymowska-Lalanne Z, 2) Carey AH, 2) Jones H, 3) Soares B, 4) Rivolta M, 4) Holley M, 1) Brown SDM
Institutions: 1)MRC Mammalian Genetics Unit and UK Mouse Genome Centre Harwell, 2)Oxagene Ltd. 3)Departments of Pediatrics and Physiology and Biophysics, University of Iowa, 4)Department of Physiology, School of Medical Sciences

We have begun to use cDNA microarrays to explore gene expression profile changes accompanying the development of the sensory neuroepithelium, the organ of Corti, in the inner ear, as well as to identify expression changes in deaf mouse mutations that affect the function of the auditory transduction apparatus. Comparative analysis of wild-type and mutants allows us to dissect the genetic pathways involved in neuroepithelial development and function.

Using two microarrays - a 5K NMIE array (established from a normalised newborn mouse inner ear cDNA library) and a 5K NIA array (made from embryonic libraries constructed by Minoru Ko, NIA, US), We have undertaken systematic comparisons of cochlea gene expression in wild-type and deaf mutant mice, including the shaker1 and whirler mutants. We have also analysed the expression profile changes of the sensory neuroepithelial cell line OC-1 before and after differentiation. A much larger number of expression differences are seen during OC-1 cell line differentiation on both arrays compared to the differences observed between wild-type and deafness mutants. Few significant changes are observed between wild-type and deafness mutants on the NIA array. However, a significant number of changes are observed on the NMIE array. Of particular interest is the discovery that the vast majority of genes up-regulated in the shaker1 mutant - a group of 40 genes in total - are all down-regulated in the mutant whirler.