ArticlePLoS genetics2014
Molecular identification of collagen 17a1 as a major genetic modifier of laminin gamma 2 mutation-induced junctional epidermolysis bullosa in mice.
Article in PLoS genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 32 citations in OpenAlex.
- Mettl3-catalyzed mScience advances · 2023Article
- Trametinib-Induced Epidermal Thinning Accelerates a Mouse Model of Junctional Epidermolysis Bullosa.Biomolecules · 2023Article
- Dystonin modifiers of junctional epidermolysis bullosa and models of epidermolysis bullosa simplex without dystonia musculorum.PloS one · 2023Article
- Functional analysis of Collagen 17a1: A genetic modifier of junctional epidermolysis bullosa in mice.PloS one · 2023Article
- Seven naturally variant loci serve as genetic modifiers of Lamc2jeb induced non-Herlitz junctional Epidermolysis Bullosa in mice.PloS one · 2023Article
- Targeted NGS in Diagnostics of Genodermatosis Characterized by the Epidermolysis Bullosa Symptom Complex in 268 Russian Children.International journal of molecular sciences · 2022Article
- BP180/Collagen XVII: A Molecular View.International journal of molecular sciences · 2021Review
- Epigenetic and metabolic regulation of epidermal homeostasis.Experimental dermatology · 2021Review
- Keratinocyte-specific deletion of SHARPIN induces atopic dermatitis-like inflammation in mice.PloS one · 2020Article
- Gain of function p.E138A alteration in Card14 leads to psoriasiform skin inflammation and implicates genetic modifiers in disease severity.Experimental and molecular pathology · 2019Article
- Identification of a Nine-Gene Signature and Establishment of a Prognostic Nomogram Predicting Overall Survival of Pancreatic Cancer.Frontiers in oncology · 2019Article
- Advances in understanding the molecular basis of skin fragility.F1000Research · 2018Review
- Skin fragility in the wild-derived, inbred mouse strain Mus pahari/EiJ.Experimental and molecular pathology · 2017Article
- Progress toward Treatment and Cure of Epidermolysis Bullosa: Summary of the DEBRA International Research Symposium EB2015.The Journal of investigative dermatology · 2016Review
- A Common Variant of PROK1 (V67I) Acts as a Genetic Modifier in Early Human Pregnancy through Down-Regulation of Gene Expression.International journal of molecular sciences · 2016Article
- Skin Diseases in Laboratory Mice: Approaches to Drug Target Identification and Efficacy Screening.Methods in molecular biology (Clifton, N.J.) · 2016Article
- Juxta-articular joint-capsule mineralization in CD73 deficient mice: similarities to patients with NT5E mutations.Cell cycle (Georgetown, Tex.) · 2014Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Epidermolysis Bullosa (EB) encompasses a spectrum of mechanobullous disorders caused by rare mutations that result in structural weakening of the skin and mucous membranes. While gene mutated and types of mutations present are broadly predictive of the range of disease to be expected, a remarkable amount of phenotypic variability remains unaccounted for in all but the most deleterious cases. This unexplained variance raises the possibility of genetic modifier effects. We tested this hypothesis using a mouse model that recapitulates a non-Herlitz form of junctional EB (JEB) owing to the hypomorphic jeb allele of laminin gamma 2 (Lamc2). By varying normally asymptomatic background genetics, we document the potent impact of genetic modifiers on the strength of dermal-epidermal adhesion and on the clinical severity of JEB in the context of the Lamc2(jeb) mutation. Through an unbiased genetic approach involving a combination of QTL mapping and positional cloning, we demonstrate that Col17a1 is a strong genetic modifier of the non-Herlitz JEB that develops in Lamc2(jeb) mice. This modifier is defined by variations in 1-3 neighboring amino acids in the non-collagenous 4 domain of the collagen XVII protein. These allelic variants alter the strength of dermal-epidermal adhesion in the context of the Lamc2(jeb) mutation and, consequentially, broadly impact the clinical severity of JEB. Overall the results provide an explanation for how normally innocuous allelic variants can act epistatically with a disease causing mutation to impact the severity of a rare, heritable mechanobullous disorder.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.