Sebaceous lipids are essential for water repulsion, protection against UVB-induced apoptosis and ocular integrity in mice
Sebaceous lipids are essential for water repulsion, protection against UVB-induced apoptosis and ocular integrity in mice
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DOI：
10.1242/dev.132753
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发表时间：
2016-05-15
期刊：
影响因子：
4.6
通讯作者：
Schneider, Marlon R.
中科院分区：
文献类型：
--
作者：
Dahlhoff, Maik;Camera, Emanuela;Schneider, Marlon R.
特征在于导致细胞破坏的脂质积聚的皮脂细胞可以在毛囊相关的皮脂腺（SG）或游离SG（例如眼睑中的睑板腺）中发现。由于缺乏允许靶向皮脂细胞同时保持完整的表皮脂质的遗传工具，因此皮脂脂质在健康和疾病中的相关性仍然知之甚少。使用仅在成熟皮脂腺细胞中表达的Scd 3，我们建立了具有皮脂腺细胞特异性表达Cre重组酶的小鼠系。RT-PCR分析和与Rosa 26-lacZ报告小鼠和Kras（G12 D）小鼠的杂交都证实了Cre特异性地在SG中的活性，而在其他皮肤区室中没有活性。重要的是，SCD 3功能的丧失不会引起可检测的表型改变，这支持了Scd 3-Cre小鼠用于进一步功能研究的有用性。Scd 3-Cre诱导的白喉链A毒素介导的皮脂脂质耗竭导致水排斥和体温调节受损，UVB诱导的表皮细胞凋亡率增加，并引起类似睑板腺功能障碍的眼表严重病理。这种新的小鼠系将有助于进一步研究皮脂脂质在皮肤和眼睛完整性中的作用。
Sebocytes, which are characterized by lipid accumulation that leads to cell disruption, can be found in hair follicle-associated sebaceous glands (SGs) or in free SGs such as the Meibomian glands in the eyelids. Because genetic tools that allow targeting of sebocytes while maintaining intact epidermal lipids are lacking, the relevance of sebaceous lipids in health and disease remains poorly understood. Using Scd3, which is expressed exclusively in mature sebocytes, we established a mouse line with sebocyte-specific expression of Cre recombinase. Both RT-PCR analysis and crossing into Rosa26-lacZ reporter mice and Kras(G12D) mice confirmed Cre activity specifically in SGs, with no activity in other skin compartments. Importantly, loss of SCD3 function did not cause detectable phenotypical alterations, endorsing the usefulness of Scd3-Cre mice for further functional studies. Scd3-Cre-induced, diphtheria chain A toxin-mediated depletion of sebaceous lipids resulted in impaired water repulsion and thermoregulation, increased rates of UVB-induced epidermal apoptosis and caused a severe pathology of the ocular surface resembling Meibomian gland dysfunction. This novel mouse line will be useful for further investigating the roles of sebaceous lipids in skin and eye integrity.