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Cited by 31Hair Growth and DisordersGenetic and rare skin diseases.Skin and Cellular Biology Research

Loss of Mpzl3 Function Causes Various Skin Abnormalities and Greatly Reduced Adipose Depots

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Leiva, Angel G., Chen, Anne L., Devarajan, Priyadharshini, Chen, Zhibin, Damanpour, Shadi, Hall, Jessica A., Bianco, Antonio C., Li, Jie +6 more·2014·Journal of Investigative Dermatology
DOI 10.1038/jid.2014.94PMC PMC4057944
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Abstract

The rough coat (rc) spontaneous mutation causes sebaceous gland (SG) hypertrophy, hair loss, and extracutaneous abnormalities including growth retardation. The rc mice have a missense mutation in the predicted Ig protein Myelin Protein Zero-Like 3 (Mpzl3). In this study, we generated Mpzl3 knockout mice to determine its functions in the skin. Homozygous Mpzl3 knockout mice showed unkempt and greasy hair coat and hair loss soon after birth. Histological analysis revealed severe SG hypertrophy and increased dermal thickness, but did not detect significant changes in the hair cycle. Mpzl3-null mice frequently developed inflammatory skin lesions; however, the early-onset skin abnormalities were not the result of immune defects. The abnormalities in the Mpzl3 knockout mice closely resemble those observed in rc/rc mice, and in mice heterozygous for both the rc and Mpzl3 knockout alleles, indicating that rc and Mpzl3 are allelic. Using a lacZ reporter gene, we detected Mpzl3 promoter activity in the companion layer and inner root sheath of the hair follicle, SG, and epidermis. Loss of MPZL3 function also caused a striking reduction in cutaneous and overall adipose tissue. These data reveal a complex role for Mpzl3 in the control of skin development, hair growth, and adipose cell functions.

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  • Mpzl3 knockout mice recapitulated the rc phenotype, and mice with white hair coat developed more severe and persistent inflammatory skin phenotype and dandruff in the seborrheic areas.

    “Our Mpzl3 knockout mice recapitulated the rc phenotype, and mice with white hair coat developed more severe and persistent inflammatory skin phenotype and dandruff in the seborrheic areas [85].”

    From Seborrheic Dermatitis and Dandruff: A Comprehensive Review (2015) · cites this paper as [85]

    The Results sections on sebaceous hypertrophy and inflammatory skin phenotype report that Mpzl3 knockout mice closely resembled rc mice and developed inflammatory lesions. They note that redness was particularly apparent in albino mice and describe scales resembling those of seborrheic dermatitis. They do not establish that white-coated mice had more severe or persistent inflammation, or specifically locate dandruff in seborrheic areas; page numbers were unavailable in our copy. (LLM, conf=0.86)

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  • Skin abnormalities in Mpzl3 knockout mice and perturbed epidermal differentiation in organotypic human skin models with MPZL3 knockdown indicate that MPZL3 is a key regulator of epidermal differentiation.

    “However, skin abnormalities in Mpzl3 knockout mice and perturbed epidermal differentiation in organotypic human skin models with MPZL3 knockdown indicate that MPZL3 is a key regulator of epidermal differentiation [85,86].”

    From Seborrheic Dermatitis and Dandruff: A Comprehensive Review (2015) · cites this paper as [85]

  • The cause of the rc phenotype is a missense mutation in the Mpzl3 gene, which is expressed in the superficial layers of the epidermis.

    “We have since identified the cause of the rc phenotype to be a missense mutation in the Mpzl3 gene, which is expressed in the superficial layers of the epidermis [84,85].”

    From Seborrheic Dermatitis and Dandruff: A Comprehensive Review (2015) · cites this paper as [85]

  • The early-onset inflammatory skin phenotype in Mpzl3 knockout mice was not caused by immune defects.

    “We have shown that the early-onset inflammatory skin phenotype was not caused by immune defects [85].”

    From Seborrheic Dermatitis and Dandruff: A Comprehensive Review (2015) · cites this paper as [85]

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Authors
Leiva, A. G., Chen, A. L., Devarajan, P., Chen, Z., Damanpour, S., Hall, J. A., Bianco, A. C., Li, J., Badiavas, E. V., Zaias, J., Miteva, M., Romanelli, P., Nouri, K., & Cao Wikramanayake, T.
Affiliations
University of Miami (US)
ORCID
Venue
Journal of Investigative Dermatology
Publisher
Elsevier BV
Published
2014-07
Volume
134
Issue
7
Pages
1817-1827
ISSN
0022-202X (ISSN-L)
DOI
10.1038/jid.2014.94
PMC
PMC4057944
OpenAlex
W1990829173
Cited by
31
References
2
Citations by year
2026: 1 · 2025: 2 · 2024: 3 · 2023: 1 · 2022: 8 · 2021: 3 · 2020: 1 · 2019: 1 · 2018: 2 · 2017: 4 · 2016: 1 · 2015: 3
FWCI
3.39
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Investigative Dermatology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Dermatology Foundation
  • University of Miami
  • Sylvester Comprehensive Cancer Center, University of Miami Health Systems
  • National Institutes of Health
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (K01AR050487, R03AR059907)
  • National Center for Research Resources
Topics
  • Health Sciences › Medicine › Urology › Hair Growth and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and rare skin diseases.
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Skin and Cellular Biology Research
Keywords
sebaceous gland hypertrophy, hair loss, skin development, adipose tissue reduction, inflammatory skin lesions, hair follicle, epidermis, knockout mice, allelic replacement
MeSH terms
Alopecia, Animals, Epidermis, Female, Flow Cytometry, Hypertrophy, Lac Operon, Male, Membrane Proteins, Mice, Inbred C57BL, Phenotype, Promoter Regions, Genetic, Sebaceous Glands, Skin Diseases, Mice, Knockout, Dermis, Subcutaneous Fat, Adiposity, Mice

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