The rough fur (<i>ruf</i>) mutation in mice is an allele of myelin protein zero-like 3 (<i>Mpzl3</i>)

Palanza, Kenneth M.; Radden, Legairre A.; Rabah, Mohammed A.; Nguyen, Tu Van; Kohm, Audra C.; Connor, Malcolm E.; Ricci, M; Stewart, Jachius J.; Eragene, Sidney; King, Thomas

doi:10.1080/23312025.2017.1370058

Cited by 3 publications

(3 citation statements)

References 20 publications

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“…Mutant mice in the C57BL/6 background show a similar inflammatory skin phenotype . Additionally, the rough fur ( ruf ) mice that carry a mutant allele of Mpzl3 in the C3H/HeJ strain background by complementation testing also show mild hyperkeratosis, although a mutation has not been identified . In addition to sebaceous hyperplasia, the Mpzl3 knockout mouse skin also showed gene expression changes consistent with aberrant epidermal differentiation .…”

Section: Other Predisposing and Causative Factorsmentioning

confidence: 99%

Seborrheic dermatitis—Looking beyond Malassezia

Wikramanayake

Borda

Miteva

et al. 2019

Experimental Dermatology

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Seborrhoeic Dermatitis (SD) is a very common chronic and/or relapsing inflammatory skin disorder whose pathophysiology remains poorly understood. Yeast of the genus Malassezia has long been regarded as a main predisposing factor, even though causal relationship has not been firmly established. Additional predisposing factors have been described, including sebaceous activity, host immunity (especially HIV infection), epidermal barrier integrity, skin microbiota, endocrine and neurologic factors, and environmental influences. Genetic studies in humans and mouse models—with particularly interesting insights from examining the Mpzl3 knockout mice and their SD‐like skin phenotype, and patients carrying a ZNF750 mutation—highlight defects in host immunity, epidermal barrier and sebaceous activity. After synthesizing key evidence from the literature, we propose that intrinsic host factors, such as changes in the amount or composition of sebum and/or defective epidermal barrier, rather than Malassezia, may form the basis of SD pathobiology. We argue that these intrinsic changes provide favourable conditions for the commensal Malassezia to over‐colonize and elicit host inflammatory response. Aberrant host immune activity or failure to clear skin microbes may bypass the initial epidermal or sebaceous abnormalities. We delineate specific future clinical investigations, complemented by studies in suitable SD animal models, that dissect the roles of different epidermal compartments and immune components as well as their crosstalk and interactions with the skin microbiota during the process of SD. This research perspective beyond the conventional Malassezia‐centric view of SD pathogenesis is expected to enable the development of better therapeutic interventions for the management of recurrent SD.

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Section: Other Predisposing and Causative Factorsmentioning

confidence: 99%

Seborrheic dermatitis—Looking beyond Malassezia

Wikramanayake

Borda

Miteva

et al. 2019

Experimental Dermatology

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“…[21,28,29] For example, elevated conversion of testosterone to the more potent dihydrotestosterone by SRD5A1 can promote SG hyperplasia, a common feature of androgenetic alopecia. [87] Interestingly, mice carrying the rough fur (ruf) allele on chromosome 9 also develop SG hypertrophy and excessive lipid deposits on skin surface, and genetic complementation with the rc mice showed that ruf is another spontaneous mutant allele of Mpzl3 [88] (Table 1), although sequence analysis of the Mpzl3 promoter, exons and splice junctions did not detect any mutant-specific DNA defect. [88] Another spontaneous mutant mouse strain, "inherited seborrheic dermatitis" (seb), develop SG hypertrophy and seborrheic dermatitis-like skin inflammation simi-lar to those observed in the Mpzl3 GKO mice, [89] but the gene mutation has not been identified.…”

Section: Mpzl3 Negatively Regulates Murine Sg Size In Development And...mentioning

confidence: 99%

Mitochondrially localized MPZL3 emerges as a signaling hub of mammalian physiology

et al. 2021

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MPZL3 is a nuclear‐encoded, mitochondrially localized, immunoglobulin‐like V‐type protein that functions as a key regulator of epithelial cell differentiation, lipid metabolism, ROS production, glycemic control, and energy expenditure. Recently, MPZL3 has surfaced as an important modulator of sebaceous gland function and of hair follicle cycling, an organ transformation process that is also governed by peripheral clock gene activity and PPARγ. Given the phenotype similarities and differences between Mpzl3 and Pparγ knockout mice, we propose that MPZL3 serves as a signaling hub that is regulated by core clock gene products and/or PPARγ to translate signals from these nuclear transcription factors to the mitochondria to modulate circadian and metabolic regulation. Conservation between murine and human MPZL3 suggests that human MPZL3 may have similarly complex functions in health and disease. We summarize current knowledge and discuss future directions to elucidate the full spectrum of MPZL3 functions in mammalian physiology.

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“…Recently, the spontaneous mutation rough fur ( ruf ) in the C3H/HeJ mouse strain was also identified as an allele of Mpzl3 . Phenotype characterization was mainly carried out in the skin and hair, and homozygous ruf mice showed unkempt and greasy hair coat, and occasionally broken hairs and mild hyperkeratosis .…”

Section: Rough Coat (Rc)mentioning

confidence: 99%

The genetic basis of seborrhoeic dermatitis: a review

Karakadze

Hirt

Wikramanayake

2017

Acad Dermatol Venereol

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Seborrhoeic Dermatitis (SD) is a common inflammatory skin disease that presents as itchy, flaking skin in the seborrhoeic areas. Various environmental and intrinsic factors have been identified as predisposing factors for SD, but its aetiology remains poorly understood. Although it was recognized that genetic factors play a role in SD aetiology, there have not been studies that systematically review the literature specifically for causal mutations or protein deficiencies in SD. In this review, we searched various databases for gene mutations and protein deficiencies that cause SD or SD-like phenotype in humans and experimental animals, and summarize 11 gene mutations or protein deficiencies that were described in the literature. Most of the encoded proteins play a role either in the immune response (ACT1, C5, IKBKG/NEMO, STK4, 2C TCR) or epidermal differentiation (ZNF750, MPZL3). Understanding the genetic basis of SD can impart knowledge of the pathobiology of the disease and help identify novel therapeutic targets.

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The rough fur (ruf) mutation in mice is an allele of myelin protein zero-like 3 (Mpzl3)

Cited by 3 publications

References 20 publications

Seborrheic dermatitis—Looking beyond Malassezia

Seborrheic dermatitis—Looking beyond Malassezia

Mitochondrially localized MPZL3 emerges as a signaling hub of mammalian physiology

The genetic basis of seborrhoeic dermatitis: a review

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