Study Reveals Complex Role of Largely Unknown Mpzl3 Gene

A multidisciplinary study led by Tongyu Cao Wikramanayake, Ph.D., research assistant professor of dermatology and cutaneous surgery, has pinpointed multiple roles of the little-known protein-coding gene Mpzl3 (myelin protein zero-like 3).

Published online ahead of print in the Journal of Investigative Dermatology, a leading journal in dermatology and skin biology, the study, “Loss of Mpzl3 Function Causes Various Skin Abnormalities and Greatly Reduced Adipose Depots,” reveals a complex role of Mpzl3 in the control of skin development, hair growth and adipose cell functions.

“To our knowledge, this is the first published comprehensive study to understand the functions of the Mpzl3 protein in the skin,” said Wikramanayake, who was senior author of the study. “This protein clearly has an important role in multiple organ systems.”

In the study, researchers linked loss of Mpzl3 function to severe skin abnormalities, such as hair loss, increased size of the sebaceous glands, increased dermal thickness and persistent inflammatory lesions. Data also revealed major deficiencies in both visceral and subcutaneous adipose tissue (50 percent total reduction), confirming a report by another group that Mpzl3 plays an important role in regulating metabolism and energy expenditure using independently generated mice.

“These mice provide a unique animal model to study not only specific organ and tissue function and cross-talk between different tissue compartments, but also related complex human diseases, such as acne, osteoporosis, and inflammatory and metabolic diseases,” said Marjana Tomic-Canic, Ph.D., professor of dermatology and cutaneous surgery and Director of the Wound Healing and Regenerative Medicine Research Program, who was not involved in the study.

Wikramanayake says the model will be used for future systematic studies to understand how Mpzl3 is involved in skin homeostasis and adipose function and metabolism, and whether its function can be modulated to treat related disorders.

The study of the gene’s multiple roles spanned six departments, divisions, institutes and centers at the Miller School. Collaborating on the study were the Department of Dermatology and Cutaneous Surgery’s Angel G. Leiva, an undergraduate student from UM’s Biology Program and Howard Hughes Medical Institute Exceptional Research Opportunities Program Scholar; third-year medical student Anne L. Chen; second-year medical student Shadi Damanpour; associate professors Jie Li, M.D., Ph.D., Paolo Romanelli, M.D., and Evangelos V. Badiavas, M.D., Ph.D., who also is a member of the Interdisciplinary Stem Cell Institute; Mariya Miteva, M.D., assistant professor, and Keyvan Nouri, M.D., professor and Chief of Dermatology Services at Sylvester Comprehensive Cancer Center, graduate student Priyadharshini Devarajan and Zhibin Chen, M.D., Ph.D., associate professor, from the Department of Microbiology and Immunology; graduate student Jessica A. Hall and Antonio C. Bianco, M.D., Ph.D., professor of medicine and Chief of the Division of Endocrinology, Diabetes and Metabolism, from the Department of Medicine; and Julia Zaias, D.V.M., Ph.D., research associate professor from the Division of Comparative Pathology.
Wikramanayake, who also is a member of the Molecular Cell and Developmental Biology Program graduate faculty and Sylvester Comprehensive Cancer Center, said the study was “truly a collaborative effort.”

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