title: Loss of Mpzl3 function causes various skin abnormalities and greatly reduced adipose depots.
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.
authors: Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA.
authors: Angel G
authors: AG
authors: Leiva
authors: Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA.
authors: Anne L
authors: AL
authors: Chen
authors: Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, Florida, USA.
authors: Priyadharshini
authors: P
authors: Devarajan
authors: Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, Florida, USA.
authors: Zhibin
authors: Z
authors: Chen
authors: Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA.
authors: Shadi
authors: S
authors: Damanpour
authors: Division of Endocrinology, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida, USA.
authors: Jessica A
authors: JA
authors: Hall
authors: Division of Endocrinology, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida, USA.
authors: Antonio C
authors: AC
authors: Bianco
authors: Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA.
authors: Jie
authors: J
authors: Li
authors: Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA; Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, Florida, USA.
authors: Evangelos V
authors: EV
authors: Badiavas
authors: Department of Pathology, University of Miami Miller School of Medicine, Miami, Florida, USA.
authors: Julia
authors: J
authors: Zaias
authors: Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA.
authors: Mariya
authors: M
authors: Miteva
authors: Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA.
authors: Paolo
authors: P
authors: Romanelli
authors: Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA.
authors: Keyvan
authors: K
authors: Nouri
authors: Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA; Molecular Cell and Developmental Biology, Graduate Program in Biomedical Sciences, University of Miami Miller School of Medicine, Miami, Florida, USA; Cancer Epidemiology and Prevention Program, Sylvester Comprehensive Cancer Center, University of Miami Health System, Miami, Florida, USA. Electronic address: tcao@med.miami.edu.
authors: Tongyu
authors: T
authors: Cao Wikramanayake
mesh_terms: D050154:Adiposity / Q000235:genetics*; D000505:Alopecia / Q000235:genetics / Q000276:immunology / Q000473:pathology; D000818:Animals; D020405:Dermis / Q000473:pathology; D004817:Epidermis / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D006984:Hypertrophy / Q000473:pathology; D007763:Lac Operon; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype; D011401:Promoter Regions, Genetic / Q000502:physiology; D012627:Sebaceous Glands / Q000473:pathology; D012871:Skin Diseases / Q000235:genetics* / Q000276:immunology / Q000473:pathology*; D050151:Subcutaneous Fat / Q000473:pathology*
chemical_list: D008565:Membrane Proteins; C520409:Mpzl3 protein, mouse