Dataset Information

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.

SUBMITTER: Leiva AG

PROVIDER: S-EPMC4057944 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

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

Leiva Angel G AG Chen Anne L AL Devarajan Priyadharshini P Chen Zhibin Z Damanpour Shadi S Hall Jessica A JA Bianco Antonio C AC Li Jie J Badiavas Evangelos V EV Zaias Julia J Miteva Mariya M Romanelli Paolo P Nouri Keyvan K Cao Wikramanayake Tongyu T

The Journal of investigative dermatology 20140214 7

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 ...[more]

PMID: 24531688

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Project description:*Background: Adipocytes mainly function as energy storage and endocrine cells. The amount and distribution of fat are important factor that influence the meat quality in the beef industry. Fat depot can be found around internal organ (ometal), beneath the skin (subcutaneous), and between muscles (intramuscular). Different adipose depot showed the biological and genetic difference depending on their location. This inter-depot variation might be influenced by the inherent genetic programing for development of adipose depots. In this study, we used RNA-seq data to investigate the difference in transcriptome of various adipose depots in Hanwoo. *Results: Using RNA-seq, we identified 5797, 2156, and 5455 DEGs in the comparison between OI, OS, and IS respectively (FDR<0.01) and found 853, 48, and 979 DEGs specific to subcutaneous, intramuscular and omental fat respectively. DEGs in intramuscular fat were highly enriched the metabolism related pathways compared to other fat depots. DEGs specific to the omental fat is significantly enriched in PPAR signaling pathway and cell-junction related pathway. In subcutaneous fat, cytokine-cytokine receptor interaction with chemokines (CXC and CC subfamily) was the most significantly enriched the pathways. Interestingly, melanogenesis pathway was associated with the subcutaneous depot. Even though the adipose tissues shared the same pathways for adipocyte differentiation, the regulation of genes were different based on the depot. *Conclusions: We comparatively analyzed the transcripome profile from different adipose tissues using NGS and identified DEGs between adipose depot and specific to depot in Hanwoo animals. The functional annotation analysis of DEGs found that transcriptome profile difference in various adipose tissue of intramuscular, subcutaneous, and ometal fat. whole mRNA sequencing profiles of nine Korean native cattle (nine profiles of omental fat tissue, nine profiles of intramuscular fat tissue, nine profiles of subcutaneous fat tissue and eight profiles of muscle tissue)

Project description:Key pointsSeveral distinct strategies produce and conserve heat to maintain the body temperature of mammals, each associated with unique physiologies, with consequences for wellness and disease susceptibility Highly regulated properties of skin offset the total requirement for heat production We hypothesize that the adipose component of skin is primarily responsible for modulating heat flux; here we evaluate the relative regulation of adipose depots in mouse and human, to test their recruitment to heat production and conservation We found that insulating mouse dermal white adipose tissue accumulates in response to environmentally and genetically induced cool stress; this layer is one of two adipose depots closely apposed to mouse skin, where the subcutaneous mammary gland fat pads are actively recruited to heat production In contrast, the body-wide adipose depot associated with human skin produces heat directly, potentially creating an alternative to the centrally regulated brown adipose tissue ABSTRACT: Mammalian skin impacts metabolic efficiency system-wide, controlling the rate of heat loss and consequent heat production. Here we compare the unique fat depots associated with mouse and human skin, to determine whether they have corresponding functions and regulation. For humans, we assay a skin-associated fat (SAF) body-wide depot to distinguish it from the subcutaneous fat pads characteristic of the abdomen and upper limbs. We show that the thickness of SAF is not related to general adiposity; it is much thicker (1.6-fold) in women than men, and highly subject-specific. We used molecular and cellular assays of β-adrenergic-induced lipolysis and found that dermal white adipose tissue (dWAT) in mice is resistant to lipolysis; in contrast, the body-wide human SAF depot becomes lipolytic, generating heat in response to β-adrenergic stimulation. In mice challenged to make more heat to maintain body temperature (either environmentally or genetically), there is a compensatory increase in thickness of dWAT: a corresponding β-adrenergic stimulation of human skin adipose (in vivo or in explant) depletes adipocyte lipid content. We summarize the regulation of skin-associated adipocytes by age, sex and adiposity, for both species. We conclude that the body-wide dWAT depot of mice shows unique regulation that enables it to be deployed for heat preservation; combined with the actively lipolytic subcutaneous mammary fat pads they enable thermal defence. The adipose tissue that covers human subjects produces heat directly, providing an alternative to the brown adipose tissues.

Dataset Information

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

Publications

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

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