Seven naturally variant loci serve as genetic modifiers of Lamc2jeb induced non-Herlitz junctional Epidermolysis Bullosa in mice.
Seven naturally variant loci serve as genetic modifiers of Lamc2jeb induced non-Herlitz junctional Epidermolysis Bullosa in mice.
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七个天然变体基因座用作LAMC2JEB的遗传修饰剂，诱导了小鼠的非纯裂性表皮溶液。
DOI：
10.1371/journal.pone.0288263
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发表时间：
2023
期刊：
影响因子：
3.7
通讯作者：
中科院分区：
文献类型：
--
作者：
Epidermolysis Bullosa (EB) is a group of rare genetic disorders that compromise the structural integrity of the skin such that blisters and subsequent erosions occur after minor trauma. While primary genetic risk of all subforms of EB adhere to Mendelian patterns of inheritance, their clinical presentations and severities can vary greatly, implying genetic modifiers. The Lamc2jeb mouse model of non-Herlitz junctional EB (JEB-nH) demonstrated that genetic modifiers can contribute substantially to the phenotypic variability of JEB and likely other forms of EB. The innocuous changes in an ‘EB related gene’, Col17a1, have shown it to be a dominant modifier of Lamc2jeb. This work identifies six additional Quantitative Trait Loci (QTL) that modify disease in Lamc2jeb/jeb mice. Three QTL include other known ‘EB related genes’, with the strongest modifier effect mapping to a region including the epidermal hemi-desmosomal structural gene dystonin (Dst-e/Bpag1-e). Three other QTL map to intervals devoid of known EB-associated genes. Of these, one contains the nuclear receptor coactivator Ppargc1a as its primary candidate and the others contain related genes Pparg and Igf1, suggesting modifier pathways. These results, demonstrating the potent disease modifying effects of normally innocuous genetic variants, greatly expand the landscape of genetic modifiers of EB and therapeutic approaches that may be applied.
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影响因子：
6.9
作者：
Has, Cristina;Nystroem, Alexander;Uitto, Jouni
通讯作者：
Uitto, Jouni
影响因子：
10.3
作者：
Kern, J. S.;Grueninger, G.;Has, C.
通讯作者：
Has, C.
影响因子：
10.3
作者：
Bolling, M. C.;Veenstra, M. J.;Bruckner, A. L.
通讯作者：
Bruckner, A. L.
DOI：
10.1111/jdv.16332
发表时间：
2020-05-22
影响因子：
9.2
作者：
Mittwollen, R.;Wohlfart, S.;Hammersen, J.
通讯作者：
Hammersen, J.
影响因子：
4
作者：
Kiritsi, Dimitra;Kern, Johannes S.;Bruckner-Tuderman, Leena
通讯作者：
Bruckner-Tuderman, Leena