New Insights into the Melanophilin (MLPH) Gene Affecting Coat Color Dilution in Rabbits.
New Insights into the Melanophilin (MLPH) Gene Affecting Coat Color Dilution in Rabbits.
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对黑色素（MLPH）基因的新见解影响兔子的外套颜色稀释。
DOI：
10.3390/genes9090430
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发表时间：
2018-08-23
期刊：
影响因子：
3.5
通讯作者：
Allain D
中科院分区：
文献类型：
--
作者：
Demars J;Iannuccelli N;Utzeri VJ;Auvinet G;Riquet J;Fontanesi L;Allain D
毛色稀释对应于导致野生型色素稀释的特定色素沉着表型。它影响含有真黑素和褐黑素的黑素体。稀释表型的遗传方式为常染色体隐性遗传。候选基因的方法集中在亲黑素（MLPH）基因突出了两个与兔稀释表型相关的变体：c.111-5C>A变体位于受体剪接位点或c.585delG变体，移码突变。在转录水平上，两个外显子的跳跃被报道为负责毛色稀释的分子机制。为了澄清这两种变体中哪一种代表因果变体，（i）我们通过对蓖麻和龙猫种群进行基因分型来分析其等位基因分离，（ii）我们评估了其对稀释或野生型毛色动物皮肤样本中MLPH转录本稳定性的功能影响。首先，我们发现c.585delG变体与内含子c.111-5C>A变体相比显示出与稀释表型的完美关联。其次，我们确定了三种不同的MLPH异构体，包括野生型异构体，外显子跳跃异构体和保留内含子异构体。第三，我们观察到毛色稀释的兔子MLPH转录水平急剧且显着下降（p值范围为10 - 03至10 - 06）。总之，我们的研究结果为毛色稀释特性带来了新的见解。
Coat color dilution corresponds to a specific pigmentation phenotype that leads to a dilution of wild type pigments. It affects both eumelanin and pheomelanin containing melanosomes. The mode of inheritance of the dilution phenotype is autosomal recessive. Candidate gene approaches focused on the melanophilin (MLPH) gene highlighted two variants associated with the dilution phenotype in rabbits: The c.111-5C>A variant that is located in an acceptor splice site or the c.585delG variant, a frameshift mutation. On the transcript level, the skipping of two exons has been reported as the molecular mechanism responsible for the coat color dilution. To clarify, which of the two variants represents the causal variant, (i) we analyzed their allelic segregation by genotyping Castor and Chinchilla populations, and (ii) we evaluated their functional effects on the stability of MLPH transcripts in skin samples of animals with diluted or wild type coat color. Firstly, we showed that the c.585delG variant showed perfect association with the dilution phenotype in contrast to the intronic c.111-5C>A variant. Secondly, we identified three different MLPH isoforms including the wild type isoform, the exon-skipping isoform and a retained intron isoform. Thirdly, we observed a drastic and significant decrease of MLPH transcript levels in rabbits with a coat color dilution (p-values ranging from 10−03 to 10−06). Together, our results bring new insights into the coat color dilution trait.
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影响因子：
2.9
作者：
Vaez, Mohsen;Follett, Sarah A.;Bed'hom, Bertrand;Gourichon, David;Tixier-Boichard, Michele;Burke, Terry
通讯作者：
Burke, Terry
影响因子：
2.4
作者：
Fontanesi, L.;Scotti, E.;Dall'Olio, S.
通讯作者：
Dall'Olio, S.
影响因子：
3.7
作者：
Lehner S;Gähle M;Dierks C;Stelter R;Gerber J;Brehm R;Distl O
通讯作者：
Distl O
影响因子：
4.4
作者：
Bed'hom B;Vaez M;Coville JL;Gourichon D;Chastel O;Follett S;Burke T;Minvielle F
通讯作者：
Minvielle F
影响因子：
4.8
作者：
Bodin, Loys;Di Pasquale, Elisa;Mulsant, Philippe
通讯作者：
Mulsant, Philippe