Generation and functional analysis of mouse models for two dominant human genodermatoses: Hydrotic Ectodermal Dysplasia (HED) and Keratitis-Ichthyosis-Deafness (KID)
Final Report Abstract
Two mouse models for two human genodermatoses were generated and characterized. The first mouse line carries the mutation connexin26S17F in the corresponding mouse gene which is characteristic for the KID syndrome (Ichthyosis Deafness Syndrome). Although this mutation is expressed in human patients in a heterozygous dominant manner, the corresponding mice exhibit only phenotypic abnormalities when the mutation is expressed homozygously. The mice show a 35 dB higher hearing threshold and a 30 to 40% lower cochlear potential. Furthermore, they exhibit hypoplasia in tail and foot epidermic. Thus, they represent a very useful model for the human KID syndrome which will be further investigated. The mouse model for hydrotic ectodermal dysplasia connexin30A88V has been generated and is currently characterized. So far, we have not seen any skin abnormality in heterozygously mutated mice. We are currently breeding homozygously mutated mice with an 87.5% C57BL/6 genetic background. We anticipate to characterize these mice in the first half of next year.
Publications
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2010. The human deafness-associated connexin30T5M mutation causes mild hearing loss and reduces biochemical coupling among cochlear non-sensory cells in knock-in mice. Hum. Mol. Gen. 19: 4759-4773
Schütz, M., Scimemi, P., Majumder, P., De Siati, R.D., Crispino, G., Rodriguez, L., Bortolozzi, M., Santarelli, R., Seydel, A., Sonntag, S., Ingham, N., Steel, K.P., Willecke, K., and Mammano, F.
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2011. The connexin26S17F mouse mutant represents a model for the human hereditary keratitis-ichthyosis deafness syndrome. Hum. Mol. Gen. 20: 28-39
Schütz, M., Auth, T., Gehrt, A., Bosen, F., Körber, I., Strenzke, N., Moser, T., and Willecke, K.
