Functional analysis of Collagen 17a1: A genetic modifier of junctional epidermolysis bullosa in mice.
Functional analysis of Collagen 17a1: A genetic modifier of junctional epidermolysis bullosa in mice.
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DOI：
10.1371/journal.pone.0292456
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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：
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作者：
Previous work strongly implicated Collagen 17a1 (Col17a1) as a potent genetic modifier of junctional epidermolysis bullosa (JEB) caused by a hypomorphic mutation (Lamc2jeb) in mice. The importance of the noncollagenous domain (NC4) of COLXVII was suggested by use of a congenic reduction approach that restricted the modifier effect to 2–3 neighboring amino acid changes in that domain. The current study utilizes TALEN and CRISPR/Cas9 induced amino acid replacements and in-frame indels nested to NC4 to further investigate the role of this and adjoining COLXVII domains both as modifiers and primary risk effectors. We confirm the importance of COLXVI AA 1275 S/G and 1277 N/S substitutions and utilize small nested indels to show that subtle changes in this microdomain attenuate JEB. We further show that large in-frame indels removing up to 1482 bp and 169 AA of NC6 through NC1 domains are surprisingly disease free on their own but can be very potent modifiers of Lamc2jeb/jeb JEB. Together these studies exploiting gene editing to functionally dissect the Col17a1 modifier demonstrate the importance of epistatic interactions between a primary disease-causing mutation in one gene and innocuous ‘healthy’ alleles in other genes.
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影响因子：
4.5
作者：
Sproule TJ;Bubier JA;Grandi FC;Sun VZ;Philip VM;McPhee CG;Adkins EB;Sundberg JP;Roopenian DC
通讯作者：
Roopenian DC
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。
影响因子：
3.7
作者：
通讯作者：
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影响因子：
2.4
作者：
Has, Cristina;Kern, Johannes S.
通讯作者：
Kern, Johannes S.
影响因子：
4
作者：
Kiritsi, Dimitra;Kern, Johannes S.;Bruckner-Tuderman, Leena
通讯作者：
Bruckner-Tuderman, Leena
DOI：
10.1007/978-1-4939-3661-8_2
发表时间：
2016-01-01
期刊：
MOUSE MODELS FOR DRUG DISCOVERY: METHODS AND PROTOCOLS, 2ND EDITION
影响因子：
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作者：
Low, Benjamin E.;Kutny, Peter M.;Wiles, Michael V.
通讯作者：
Wiles, Michael V.