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

Angel G. Leiva; Anne L. Chen; Priyadharshini Devarajan; Zhibin Chen; Shadi Damanpour; Jessica A. Hall; Antonio C. Bianco; Jie Li; Evangelos V. Badiavas; Julia Zaias; Mariya Miteva; Paolo Romanelli; Keyvan Nouri; Tongyu Cao Wikramanayake

doi:10.1038/jid.2014.94

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

Angel G. Leiva, Anne L. Chen, Priyadharshini Devarajan, Zhibin Chen, Shadi Damanpour, Jessica A. Hall, Antonio C. Bianco, Jie Li, Evangelos V. Badiavas, Julia Zaias, Mariya Miteva, Paolo Romanelli, Keyvan Nouri, Tongyu Cao Wikramanayake^*

^*Corresponding author for this work

Dermatology

Research output: Contribution to journal › Article › peer-review

23 Scopus citations

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.

Original language	English (US)
Pages (from-to)	1817-1827
Number of pages	11
Journal	Journal of Investigative Dermatology
Volume	134
Issue number	7
DOIs	https://doi.org/10.1038/jid.2014.94
State	Published - Jul 2014

Funding

This work was supported by NIH/NIAMS grants K01AR050487 and R03AR059907 (TCW), a Dermatology Foundation Research Grant (TCW), and the Dermatology Gift Fund, University of Miami (TCW). The Mpzl3 knockout mouse strain generated for this research project was created from embryonic stem cell lines obtained from the NCRR-NIH-supported KOMP Repository ( http://www.komp.org ) at the University of California, Davis. Mouse embryonic stem cell expansion and blastocyst injections were carried out at the University of Miami Sylvester Comprehensive Cancer Center Transgenic Animal Core Facility (director: Peter Sobieszczuk, PhD). The mouse anti-Dsg 1/2 and 3 antibodies (Progen Biotechnik, Heidelberg, Germany) were kindly provided by Dr Lisa R Plano, University of Miami. TCW is very grateful for the mentoring received from Dr Katalin Csiszar (University of Hawaii at Manoa). She also thanks Anika JW and Athula HW. The authors thank Dr Lawrence A Schachner for his support and Drs Carmen I Perez, Juana Alonso, Luis Rodriguez-Menocal, and Assuan Lens and Irene A Tabas for technical assistance.

ASJC Scopus subject areas

Biochemistry
Molecular Biology
Dermatology
Cell Biology

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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. (2014). Loss of Mpzl3 function causes various skin abnormalities and greatly reduced adipose depots. Journal of Investigative Dermatology, 134(7), 1817-1827. https://doi.org/10.1038/jid.2014.94

@article{9fa62163309a4222929d797883dfad44,

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.",

author = "Leiva, {Angel G.} and Chen, {Anne L.} and Priyadharshini Devarajan and Zhibin Chen and Shadi Damanpour and Hall, {Jessica A.} and Bianco, {Antonio C.} and Jie Li and Badiavas, {Evangelos V.} and Julia Zaias and Mariya Miteva and Paolo Romanelli and Keyvan Nouri and {Cao Wikramanayake}, Tongyu",

note = "Funding Information: This work was supported by NIH/NIAMS grants K01AR050487 and R03AR059907 (TCW), a Dermatology Foundation Research Grant (TCW), and the Dermatology Gift Fund, University of Miami (TCW). The Mpzl3 knockout mouse strain generated for this research project was created from embryonic stem cell lines obtained from the NCRR-NIH-supported KOMP Repository ( http://www.komp.org ) at the University of California, Davis. Mouse embryonic stem cell expansion and blastocyst injections were carried out at the University of Miami Sylvester Comprehensive Cancer Center Transgenic Animal Core Facility (director: Peter Sobieszczuk, PhD). The mouse anti-Dsg 1/2 and 3 antibodies (Progen Biotechnik, Heidelberg, Germany) were kindly provided by Dr Lisa R Plano, University of Miami. TCW is very grateful for the mentoring received from Dr Katalin Csiszar (University of Hawaii at Manoa). She also thanks Anika JW and Athula HW. The authors thank Dr Lawrence A Schachner for his support and Drs Carmen I Perez, Juana Alonso, Luis Rodriguez-Menocal, and Assuan Lens and Irene A Tabas for technical assistance. ",

year = "2014",

month = jul,

doi = "10.1038/jid.2014.94",

language = "English (US)",

volume = "134",

pages = "1817--1827",

journal = "Journal of Investigative Dermatology",

issn = "0022-202X",

publisher = "Elsevier B.V.",

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}

Leiva, AG, Chen, AL, Devarajan, P, Chen, Z, Damanpour, S, Hall, JA, Bianco, AC, Li, J, Badiavas, EV, Zaias, J, Miteva, M, Romanelli, P, Nouri, K & Cao Wikramanayake, T 2014, 'Loss of Mpzl3 function causes various skin abnormalities and greatly reduced adipose depots', Journal of Investigative Dermatology, vol. 134, no. 7, pp. 1817-1827. https://doi.org/10.1038/jid.2014.94

TY - JOUR

T1 - Loss of Mpzl3 function causes various skin abnormalities and greatly reduced adipose depots

AU - Leiva, Angel G.

AU - Chen, Anne L.

AU - Devarajan, Priyadharshini

AU - Chen, Zhibin

AU - Damanpour, Shadi

AU - Hall, Jessica A.

AU - Bianco, Antonio C.

AU - Li, Jie

AU - Badiavas, Evangelos V.

AU - Zaias, Julia

AU - Miteva, Mariya

AU - Romanelli, Paolo

AU - Nouri, Keyvan

AU - Cao Wikramanayake, Tongyu

N1 - Funding Information: This work was supported by NIH/NIAMS grants K01AR050487 and R03AR059907 (TCW), a Dermatology Foundation Research Grant (TCW), and the Dermatology Gift Fund, University of Miami (TCW). The Mpzl3 knockout mouse strain generated for this research project was created from embryonic stem cell lines obtained from the NCRR-NIH-supported KOMP Repository ( http://www.komp.org ) at the University of California, Davis. Mouse embryonic stem cell expansion and blastocyst injections were carried out at the University of Miami Sylvester Comprehensive Cancer Center Transgenic Animal Core Facility (director: Peter Sobieszczuk, PhD). The mouse anti-Dsg 1/2 and 3 antibodies (Progen Biotechnik, Heidelberg, Germany) were kindly provided by Dr Lisa R Plano, University of Miami. TCW is very grateful for the mentoring received from Dr Katalin Csiszar (University of Hawaii at Manoa). She also thanks Anika JW and Athula HW. The authors thank Dr Lawrence A Schachner for his support and Drs Carmen I Perez, Juana Alonso, Luis Rodriguez-Menocal, and Assuan Lens and Irene A Tabas for technical assistance.

PY - 2014/7

Y1 - 2014/7

N2 - 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.

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

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