PROGRAMM JAHRESTAGUNG 2012 30. Nov. – 2. Dez ... - ÖGDV

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