PROGRAMM JAHRESTAGUNG 2012 30. Nov. – 2. Dez ... - ÖGDV
PROGRAMM JAHRESTAGUNG 2012 30. Nov. – 2. Dez ... - ÖGDV
PROGRAMM JAHRESTAGUNG 2012 30. Nov. – 2. Dez ... - ÖGDV
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Poster Gemischtes<br />
P 24<br />
DNase2 is essential for DNA degradation during holocrine secretion of sebum<br />
Heinz Fischer 1<br />
Minoo Ghannadan 1<br />
Maria Buchberger 1<br />
Judith Fumicz 1<br />
Erwin Tschachler 1<br />
Leopold Eckhart 1<br />
1 Medical University of Vienna, Department of Dermatology, Research Division of<br />
Biology and Pathobiology of the Skin, Vienna<br />
Introduction: Sebaceous glands produce sebum by holocrine secretion, which<br />
represents a special form of programmed cell death. Nuclear structures and DNA are<br />
degraded by an unknown mechanism in terminally differentiated sebocytes. To<br />
investigate the process of nuclear DNA breakdown in sebaceous glands, we have<br />
generated mice lacking the acid endonuclease, DNase 2, in keratinocytes and<br />
sebocytes.<br />
Methods: Mice carrying floxed alleles of the Dnase2a gene were crossed with mice<br />
expressing the Cre recombinase under the control of the K14 promoter to delete DNase<br />
2 in all tissues derived from K14-positive precursors, including the epidermis and the<br />
sebaceous glands. DNase activities of eluates from the stratum corneum and from the<br />
hair surface were determined in vitro using phage DNA as substrate. Residual DNA in<br />
the sebum was quantified by real time PCR. Thin sections were labeled with the DNAspecific<br />
fluorescent dye Hoechst 33258.<br />
Results: While the epidermis appeared normal, the sebaceous glands of DNase<br />
2-deficient mice contained aberrantly large amounts of DNA which localized to the<br />
most differentiated sebocytes. Eluates from the surface of wildtype hair readily<br />
degraded DNA whereas eluates from DNase 2-deficient mice lacked acid DNase activity.<br />
These data demonstrate that DNase 2 is the main acid DNase of the sebum and that its<br />
activity is required for the removal of nuclear DNA from terminally differentiated<br />
sebocytes.<br />
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