Loss of Mpzl3 function causes various skin abnormalities and greatly reduced adipose depots

J Invest Dermatol. 2014 Jul;134(7):1817-1827. doi: 10.1038/jid.2014.94. Epub 2014 Feb 14.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiposity / genetics*
  • Alopecia / genetics
  • Alopecia / immunology
  • Alopecia / pathology
  • Animals
  • Dermis / pathology
  • Epidermis / pathology
  • Female
  • Flow Cytometry
  • Hypertrophy / pathology
  • Lac Operon
  • Male
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Phenotype
  • Promoter Regions, Genetic / physiology
  • Sebaceous Glands / pathology
  • Skin Diseases / genetics*
  • Skin Diseases / immunology
  • Skin Diseases / pathology*
  • Subcutaneous Fat / pathology*


  • Membrane Proteins
  • Mpzl3 protein, mouse