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Updated: Jun 1, 2026
10:51
Isolation and Culture of Primary Mouse Keratinocytes from Neonatal and Adult Mouse Skin
Published on: July 14, 2017
SHARPIN regulates mitochondria-dependent apoptosis in keratinocytes.
Yanhua Liang1, John P Sundberg
1Department of Dermatology Yale School of Medicine, New Haven, CT 06510-3221, USA. liangdoctor@163.com
Journal of Dermatological Science
|May 31, 2011
Summary
SHARPIN deficiency in mice causes chronic proliferative dermatitis and increased keratinocyte apoptosis. This cell death is mediated by the intrinsic mitochondrial pathway involving caspases.
Area of Science:
- Dermatology
- Molecular Biology
- Cell Biology
Background:
- Chronic proliferative dermatitis mutation (CPDM) in mice results from Sharpin deficiency (Sharpin(cpdm)), leading to a multisystem disorder.
- Affected tissues exhibit eosinophilia and infiltration, with epidermal keratinocytes undergoing apoptosis, vesicle formation, and ulceration.
Purpose of the Study:
- To elucidate the molecular mechanisms driving keratinocyte apoptosis in Sharpin-deficient mice.
Main Methods:
- Comparative analysis of 10-week-old Sharpin(cpdm) and wildtype mice.
- Transmission electron microscopy for ultrastructural skin analysis.
- In vitro and in vivo assays to investigate mitochondrial pathways.
Main Results:
- Sharpin(cpdm) mice showed significantly higher rates of apoptotic skin cells (77.5%) compared to wildtype (18.1%).
- Mitochondria in Sharpin(cpdm) keratinocytes displayed disrupted structure and membrane potential loss.
- Increased BAX/BCL2 ratio and elevated caspase-9 and caspase-3 activity were observed, with caspase-3 cleavage in mutant mice.
Conclusions:
- Keratinocyte apoptosis in Sharpin(cpdm) mice is regulated by an intrinsic, caspase-dependent mitochondrial pathway.
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