International Mammalian Genome Society

The 15th International Mouse Genome Conference (2001)


Prof. Steve Brown
MRC Mammalian Genetics Unit and Mouse Genome Centre
Oxfordshire OX11 ORD UK

Co-Authors: 1)Hardisty R, 2)Erven A, 1)Tsai H, 1)Logan K, 1)Morse S, 1)Brooker D, 3)Guionaud S, 3)Sancho-Oliver S, 4)Hunter AJ, 2)Steel KP
Institutions:   1)MRC Mammalian Genetics Unit and Mouse Genome Centre, 2)MRC Institute of Hearing Research, 3)Frimorpho Ltd, 4)GlaxoSmithKline   

Otitis media is the most common cause of hearing impairment in children. There is evidence from the human population of a significant genetic component predisposing to OME. A genome wide phenotype driven ENU mutagenesis approach has been undertaken to recover, among others, novel dominantly inherited single locus deafness disorders. The Jeff mouse showed an absent Preyer response at P35. Jeff mice also display mild craniofacial abnormalities and reduced body weight. Jeff mice had pus and fluid in the middle ear (ME) cavity while the ossicles and inner ear structures were normal. Jeff showed raised threshholds for a cochlear nerve response. Histological analysis of newborn Jeff pups showed disturbance of the ME epithelia. Detailed phenotypic analyses of the ME cavity of adult Jeff mice revealed a chronic proliferative OME with severe disruption of the ME cavity epithelium, accompanied by dense granulocytic or watery effusions. Newborn and adult mice showed a narrowing of the Eustachian tube. Mice re-derived into pathogen free conditions continued to exhibit OME possibly indicative of a constitutive inflammatory response not requiring infection as a trigger. The Jeff mutant is fully penetrant and has been mapped between Six2 and D17Mit221 on mouse chromosome 17. The Jeff mutation identifies a novel locus involved in OME predisposition, and will allow us to uncover the genetic basis for at least one major aetiological factor in OME.

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