劉 杰 劉 毅 胡彥競(jìng)科 何大乾 劉安芳

(1.西南大學(xué)榮昌校區(qū)，重慶 402460；2.上海市農(nóng)業(yè)科學(xué)院，上海 201106)

動(dòng)物黑色素沉著基因KIT和MLPH的研究進(jìn)展*

劉 杰1,2劉 毅2胡彥競(jìng)科1何大乾2劉安芳1

(1.西南大學(xué)榮昌校區(qū)，重慶 402460；2.上海市農(nóng)業(yè)科學(xué)院，上海 201106)

動(dòng)物不同的膚色和被毛顏色與黑色素沉著的種類和數(shù)量有關(guān)，而黑色素的沉著需要眾多基因的參與，涉及KIT和MLPH基因等，前者在黑色素的生成過程中發(fā)揮重要的作用，后者在黑素小體轉(zhuǎn)運(yùn)的過程中具有關(guān)鍵的作用。先前的研究表明，KIT基因的突變，導(dǎo)致動(dòng)物被毛顏色的改變，同時(shí)，KIT基因突變還與人類疾病有關(guān)；MLPH基因的變異影響動(dòng)物被毛的顏色，導(dǎo)致動(dòng)物被毛顏色變淡。本文主要對(duì)黑素細(xì)胞的形成、黑色素的合成、黑色素的轉(zhuǎn)運(yùn)和KIT及 MLPH基因的研究進(jìn)行概述，旨在為黑色素沉著機(jī)制、動(dòng)物皮膚和被毛的著色研究提供參考。

KIT基因；MLPH基因；黑色素；黑素小體

動(dòng)物有不同的膚色和被毛顏色是由于黑色素沉著的種類和數(shù)量不同，因此產(chǎn)生了豐富多彩的表型。在脊椎動(dòng)物中，皮膚和被毛的著色產(chǎn)生多種多樣的表型性狀，具有偽裝、求偶、交流、警告或者恐嚇捕食者及物種識(shí)別等功能[1-2]。對(duì)于人類，皮膚中的黑色素具有光保護(hù)作用，可以防止紫外線滲透進(jìn)入皮膚表皮層，同時(shí)清除氧化反應(yīng)產(chǎn)生的自由基，以免氧化損傷DNA[3]。動(dòng)物黑色素沉著的變異是顯而易見的表型性狀[4]，可以通過構(gòu)建模式動(dòng)物去研究復(fù)雜性狀，揭示基因型與表型的密切關(guān)系[5]。

眾多的基因調(diào)控黑色素的沉著，使動(dòng)物的皮膚和被毛呈現(xiàn)不同的顏色。至今，大約有150個(gè)基因參與毛色的形成[2]，包括v-kit Hardy-Zuckerman 4貓科肉瘤病毒致癌基因同源物(the v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog, KIT)和黑素親和素(melanophilin, MLPH)等。KIT是酪氨酸蛋白激酶受體家族中的重要成員之一，其配體是干細(xì)胞生長(zhǎng)因子[6]和肥大細(xì)胞生長(zhǎng)因子[7]，在黑色素的生成、造血作用、配子形成及肥大細(xì)胞發(fā)育的過程中發(fā)揮重要作用。同時(shí)，KIT及其配體的缺失或變異導(dǎo)致紅細(xì)胞和白細(xì)胞缺乏、色素減退及不育[8-9]。MLPH、小GTP結(jié)合蛋白(Rab27a)和肌球蛋白Va(Myosin Va，Myo5a)形成三元復(fù)合物[10]，在黑素小體轉(zhuǎn)運(yùn)的過程中具有關(guān)鍵作用，使黑素小體在黑素細(xì)胞樹突末梢聚集，實(shí)現(xiàn)黑素小體從黑素細(xì)胞轉(zhuǎn)移至鄰近的角質(zhì)細(xì)胞，但是MLPH的突變會(huì)影響黑素小體的轉(zhuǎn)運(yùn)過程，使動(dòng)物毛色或羽色變淡。

1 黑色素沉著概述

黑色素沉著主要包括以下幾個(gè)方面：在發(fā)育過程中，成黑素細(xì)胞遷移到特定的組織；成黑素細(xì)胞的存活及分化成黑素細(xì)胞；黑素細(xì)胞的密度；酶的功能和黑素小體結(jié)構(gòu)的成熟；不同類型的黑色素合成；黑素小體轉(zhuǎn)運(yùn)的黑色素在鄰近的角質(zhì)細(xì)胞中的分布[11]。

1.1 黑素細(xì)胞的形成

在胚胎發(fā)育的過程中，黑素細(xì)胞由成黑素細(xì)胞增殖、分化而來(lái)[5]。成黑素細(xì)胞來(lái)源于神經(jīng)嵴細(xì)胞，通過背外側(cè)途徑遷移到皮膚表皮和毛囊。先前的研究表明，老鼠黑素細(xì)胞在妊娠中期開始發(fā)育，即胚胎的8.5～9.5d。在胚胎的8.5d成黑素細(xì)胞開始增殖，隨后在胚胎的11.5～15.5d，成黑素細(xì)胞大量增殖并遷移覆蓋整個(gè)胚胎，最后在胚胎的15.5d，成黑素細(xì)胞朝著初生毛囊的基質(zhì)遷移，其中一部分成黑素細(xì)胞形成黑素細(xì)胞干細(xì)胞，另一部分遷移到毛囊分化為成熟的黑素細(xì)胞[12]。黑素細(xì)胞干細(xì)胞是靜止期細(xì)胞，停留在初生毛囊的底層膨大部位。當(dāng)下一個(gè)生長(zhǎng)周期到來(lái)時(shí)，黑素細(xì)胞干細(xì)胞開始增殖，產(chǎn)生黑素細(xì)胞前提細(xì)胞，即成黑素細(xì)胞[13-14]。成黑素細(xì)胞又分化為成熟的黑素細(xì)胞，開始合成黑色素，通過黑素小體轉(zhuǎn)運(yùn)至鄰近的角質(zhì)細(xì)胞，實(shí)現(xiàn)黑色素的沉著，使動(dòng)物皮膚和被毛的呈現(xiàn)不同的顏色。Peter等人研究表明，KIT/干細(xì)胞因子信號(hào)通路與黑素細(xì)胞的存活、遷移和分化有關(guān)，c-KIT的表達(dá)是成黑素細(xì)胞遷移到毛囊上皮的前提條件[15]。

1.2 黑色素的合成

黑素細(xì)胞中的黑素小體是一種溶酶體相關(guān)細(xì)胞器，是合成黑色素的唯一場(chǎng)所。在黑素小體中合成真黑素和褐黑素，前者呈現(xiàn)黑色或棕色，例如黑色頭發(fā)；后者呈現(xiàn)紅色或黃色，例如紅色的頭發(fā)。

黑色素的合成是酪氨酸酶催化體內(nèi)酪氨酸羥化而啟動(dòng)的一系列生化反應(yīng)過程。參與黑色素合成的酶有酪氨酸酶( tyrosinase,TYR)、酪氨酸酶相關(guān)蛋白1( tyrosinase-related protein 1，TYRP1)和多巴色素互變異構(gòu)酶(DOPAchrome tautomerase，DCT)，其功能紊亂會(huì)導(dǎo)致黑色素沉著失調(diào)[16]。體內(nèi)酪氨酸在TYR催化下生成3,4-二羥基苯丙氨酸(Dopa，多巴)，多巴進(jìn)一步氧化生成多巴醌(DQ)。當(dāng)多巴醌與半胱氨酸(Cys)結(jié)合后生成半胱氨酸多巴(Cys-dopa)，經(jīng)氧化反應(yīng)和多聚化反應(yīng)，生成褐黑素。當(dāng)黑素小體內(nèi)缺乏半胱氨酸，過多的多巴醌環(huán)化形成多巴色素，隨后脫羧形成5,6-二羥基吲哚(DHI)，經(jīng)氧化和聚合反應(yīng)形成真黑素。如果體內(nèi)有多巴色素互變異構(gòu)酶，多巴色素羥化為5,6-二羥基吲哚羧酸(DHICA)，也形成真黑素[11,17-18]。

1.3 黑素小體的轉(zhuǎn)運(yùn)

黑素小體的形成、成熟和轉(zhuǎn)運(yùn)是色素沉著的關(guān)鍵[16]。黑素細(xì)胞中成熟的黑素小體通過微管運(yùn)送到樹突末梢，隨后轉(zhuǎn)移到相鄰的角質(zhì)細(xì)胞。黑素小體在黑素細(xì)胞中沿著微管做雙向運(yùn)動(dòng)，直到黑素小體在樹突末梢被捕獲。黑素小體在微管和黑素細(xì)胞外周的運(yùn)動(dòng)分為長(zhǎng)距離運(yùn)動(dòng)和短距離運(yùn)動(dòng)，前者需要驅(qū)動(dòng)蛋白和動(dòng)力蛋白的參與，后者需要Rab27a、MLPH和myosin Va三元復(fù)合物的參與[19]，其中任何一個(gè)蛋白的改變，會(huì)擾亂黑素小體的分布，影響黑色素的轉(zhuǎn)運(yùn)。以驅(qū)動(dòng)蛋白超家族為動(dòng)力馬達(dá)，黑素小體向著位于周邊的微管正端運(yùn)動(dòng)；在細(xì)胞質(zhì)動(dòng)力蛋白的作用下，黑素小體向位于細(xì)胞中心的微管負(fù)端運(yùn)動(dòng)。當(dāng)黑素小體到達(dá)黑素細(xì)胞外周時(shí)，黑素小體與肌動(dòng)蛋白微絲相互作用，使黑素小體在樹突末梢聚集[10,20]。

雖然通過大量的試驗(yàn)研究，但人們對(duì)黑素小體從黑素細(xì)胞樹突末梢轉(zhuǎn)運(yùn)到相鄰角質(zhì)細(xì)胞的機(jī)制知之甚少[21]。目前有關(guān)黑素小體轉(zhuǎn)運(yùn)至角質(zhì)細(xì)胞的機(jī)制存在4種假說：一是黑素細(xì)胞的樹突末梢被角質(zhì)細(xì)胞吞噬；二是基于黑素細(xì)胞的胞外分泌；三是黑素細(xì)胞質(zhì)膜和角質(zhì)細(xì)胞質(zhì)膜融合，使細(xì)胞與細(xì)胞之間形成一個(gè)通道，實(shí)現(xiàn)黑素小體的轉(zhuǎn)運(yùn)；四是黑色素從黑素細(xì)胞到角質(zhì)細(xì)胞的轉(zhuǎn)運(yùn)依賴于膜囊泡的出現(xiàn)[19,22-23]。

2 KIT基因的研究進(jìn)展

KIT是典型的Ⅲ型酪氨酸蛋白激酶受體家族的重要成員之一，由胞外域、跨膜片段、近膜域和蛋白激酶區(qū)域組成[8-9]。KIT及其配體的變異，導(dǎo)致黑色素的生成、造血作用和配子形成障礙[2]。在老鼠、豬和馬的研究中，報(bào)道了許多KIT基因突變引起的動(dòng)物被毛的改變，而人類KIT與多種疾病有關(guān)。

c-KIT功能獲得性突變與人類腫瘤有關(guān)，包括睪丸生殖細(xì)胞癌、急性骨髓白血病、胃腸道間質(zhì)瘤和肥大細(xì)胞瘤[8,24-25]。斑駁病是常染色體顯性遺傳病，由于KIT蛋白在第664個(gè)氨基酸處發(fā)生Gly→Arg的氨基酸替換，使病人皮膚出現(xiàn)斑塊和頭發(fā)毛囊完全缺乏黑素細(xì)胞[26]。黑素瘤是嚴(yán)重威脅人類健康的惡性腫瘤，KIT的表達(dá)可能與人類惡性黑素瘤的發(fā)生有關(guān)，其有可能成為治療黑素瘤的有效靶向分子之一[27]。

對(duì)于鼠科動(dòng)物，KIT信號(hào)對(duì)黑素細(xì)胞的增殖、分化、遷移及存活是必須的[28]。c-KIT基因是老鼠白色斑點(diǎn)(White Spotting ,W)基因座的候選基因，W基因座的突變對(duì)胚胎發(fā)育和造血作用具有多效性。W基因座的突變使老鼠毛色呈現(xiàn)白色、不育和不同程度貧血[29-30]。KIT基因是引起豬毛色變異的主要基因，表現(xiàn)為顯性白、黑斑及白環(huán)帶，分別由等位基因I、IP、IBe控制[31-32]。豬的顯性白是由于皮膚中缺乏黑素細(xì)胞，其原因可能與KIT基因的另一轉(zhuǎn)錄本密切相關(guān)[33]，這與Naohikod[34]等的研究結(jié)果不一致。In Cheol Cho等運(yùn)用全基因組掃描了長(zhǎng)白豬和韓國(guó)本地豬雜交的毛色遺傳，在啟動(dòng)子區(qū)、編碼區(qū)和3′非翻譯區(qū)檢測(cè)到了KIT基因的突變和缺失，提出KIT基因可作為豬毛色遺傳的候選基因[35]。Marklund等研究表明，KIT基因是馬雜毛色(Roan,Rn)和顯性花斑性狀(Tobiano,To)的一個(gè)主要候選基因，KIT基因序列多態(tài)與Rn等位基因之間存在顯著的連鎖不平衡[36]。而馬的Sabino表型可能與KIT基因外顯子17的跳躍有關(guān)[37]。Haase等的研究檢測(cè)出7個(gè)新的KIT基因突變，包括2個(gè)移碼突變、2個(gè)錯(cuò)義突變和3個(gè)剪切位點(diǎn)突變，表明馬的白色毛呈現(xiàn)出非常重要的等位基因異質(zhì)性[38]。全基因組關(guān)聯(lián)分析表明，KIT基因和小眼相關(guān)轉(zhuǎn)錄因子是控制白色毛的主要基因座，KIT或小眼相關(guān)轉(zhuǎn)錄因子的突變可能會(huì)影響馬白色毛的分布[39]。

3 MLPH基因的研究進(jìn)展

MLPH與成熟黑素小體的轉(zhuǎn)運(yùn)有關(guān)，只有黑素小體從黑素細(xì)胞轉(zhuǎn)運(yùn)到周圍的角質(zhì)細(xì)胞才能實(shí)現(xiàn)黑色素在皮膚和被毛中的著色。成熟黑素小體的轉(zhuǎn)運(yùn)需要完整的MLPH功能結(jié)構(gòu)域，即外顯子F結(jié)合域、與Myosin Va結(jié)合的卷曲螺旋區(qū)域和與Rab27a結(jié)合的突觸結(jié)合蛋白同源結(jié)構(gòu)域[40]。

大量的研究表明，MLPH基因的變異影響動(dòng)物毛色和羽色的形成。鳥類淡紫色羽的產(chǎn)生是由于真黑素和褐黑素被稀釋，而MLPH基因核苷酸的錯(cuò)義突變(C→T)與雞羽色稀釋(淡紫色羽變異)有關(guān)[41]，而鵪鶉羽色稀釋與MLPH外顯子1單堿基對(duì)的突變有關(guān)[42]。在哺乳動(dòng)物狗、貓、兔子和水貂中，MLPH基因的突變也出現(xiàn)毛色稀釋現(xiàn)象，但MLPH突變形式存在很大的差異。MLPH基因外顯子7的突變，可能是雜合子的德國(guó)賓莎犬出現(xiàn)毛色稀釋的原因，杜賓犬的毛色稀釋是由于MLPH基因外顯子2周圍的單核苷酸多態(tài)，說明一個(gè)或多個(gè)MLPH基因位點(diǎn)的突變與毛色稀釋密切相關(guān)[43]。隨后，Dr?gemülle等研究表明犬的毛色稀釋與MLPH基因外顯子1最后一個(gè)核苷酸突變(A→G)有關(guān)，同時(shí)A等位基因突變會(huì)降低MLPH基因的剪切效率[44]。Ishida等人在家貓的轉(zhuǎn)錄本外顯子2上發(fā)現(xiàn)了一個(gè)單堿基缺失，使其下游的11個(gè)氨基酸殘基提前出現(xiàn)終止密碼子，導(dǎo)致大部分MLPH蛋白被切斷，使家貓毛色變淡[45]。兔子毛色變淡是由于MLPH基因內(nèi)含子2多聚嘧啶序列剪切受體突變，使外顯子3和外顯子4跳躍，使氨基酸殘基提前出現(xiàn)終止密碼，產(chǎn)生截短蛋白[46]。Cirera等為培育銀灰色、紫色水貂，對(duì)MLPH基因進(jìn)行研究表明，銀灰色表型缺失外顯子8，導(dǎo)致肌動(dòng)蛋白結(jié)合域的缺失，影響黑素小體的轉(zhuǎn)運(yùn)及黑色素沉著，而缺失MYO5A結(jié)合域是導(dǎo)致水貂產(chǎn)生銀灰色稀釋表型的主要原因[47]。

綜上所述，黑素細(xì)胞由成黑素細(xì)胞增殖、分化而來(lái)，黑素細(xì)胞中的黑素小體是合成黑色素的唯一場(chǎng)所，攜帶黑色素顆粒的成熟黑素小體被轉(zhuǎn)運(yùn)到相鄰的角質(zhì)細(xì)胞，最終調(diào)控動(dòng)物皮膚和被毛的顏色。KIT基因?qū)谒丶?xì)胞的存活、遷移和分化具有重要意義，KIT基因的突變使動(dòng)物的皮膚和被毛顏色改變。MLPH基因在黑素小體的轉(zhuǎn)運(yùn)過程中發(fā)揮重要的調(diào)控作用，其變異會(huì)使黑素小體轉(zhuǎn)運(yùn)發(fā)生障礙。KIT和MLPH基因在動(dòng)物皮膚和被毛著色的過程中具有重要作用。

[1] Braasch I,Schartl M,Volff J N.Evolution of pigment synthesis pathways by gene and genome duplication in fish[J].BMC Evolutionary Biology,2007,7:74.

[2] Reissmann M,Ludwig A.Pleiotropic effects of coat colour-associated mutations in humans, mice and other mammals[J].Seminars in Cell and Developmental Biology,2013,24:576-586.

[3] Kadekaro A L,Kavanagh R J,Wakamatsu K,etal.Cutaneous Photobiology .The Melanocyte vs . the sun :who will win the Final Round? [J].Pigment Cell Res,2003,16:434-447.

[4] Hofreiter M,Neberg T.The genetic and evolutionary basis of colour variation in vertebrates[J].Cellular and Molecular Life Sciences,2010,67:2591-2603.

[5] Hayes B J,Pryce J,Chamberlain A J,etal.Genetic Architecture of Complex Traits and Accuracy of Genomic Prediction Coat Colour, Milk-Fat Percentage, and Type in Holstein Cattle as Contrasting Model Traits[J].Plos Genetics,2010,6(9):e1001139.

[6] Grabbe J,Welker P,Dippel E,etal.Stem cell factor, a novel cutaneous growth factor for mast cells and melanocytes[J].Arch Dermatol Res,1994,287:78-84.

[7] Williams D E,Eisenman J,Baird A,etal.Identification of a ligand for the c-kit proto-oncogene[J].cell,1990,63:167-174.

[8] Robert Roskoshi Jr.Signaling by kit protein-tyrosine kinase-The stem cell factor receptor[J].Biochemical and Biophysical Research Communication,2005,337:1-13.

[9] Robert Roskoshi Jr.Structure and regulation of kit protein-tyrosine kinase-The stem cell factor receptor[J].Biochemical and Biophysical Research Communication,2005,338:1307-1315.

[10]Hume A N,Ushakov D S,Tarafder A K,etal.Rab27a and MyoVa are the primary Mlph interactors regulating melanosome transport in melanocytes[J].Journal of Cell Science,2007,120(17):3111-3122.

[11]Yamaguchi Yuji,Brenner M,Hearing V J.The Regulation of Skin Pigmentation[J].the Journal of Biological Chemistry,2007,282:27557-27561.

[12]Larue L,Vuyst F D,Delmas V.Modeling melanoblast development[J].Cellular and Molecular Life Sciences,2013,70:1067-1079.

[13]Sarin K Y,Artandi S E.Aging, Graying and Loss of Melanocyte Stem Cells[J].Stem Cell Rev,2007,3:212-217.

[14]Silver D L,Hou Ling,Pavan W J.The Genetic Regulation of Pigment Cell Development[M].Neural Crest Induction and Differentiation,2006,589:155-169.

[15]Peter Eva M J,Tobin D J, Botchkareva N. Migration of melanoblasts into the developing murine hair follicle is accompanied by transient c-Kit expression[J].the Journal of Histochemistry and cytochemistry,2002,50(6):751-766.

[16]Jennifer Y. Lin, David E. Fisher. Melanocyte biology and skin pigmentation[J].Nature,445,2007:843-850.

[17]伍革民，彭光旭.動(dòng)物黑色素研究進(jìn)展[J].甘肅畜牧獸醫(yī)，2005,35(1)：39-41.

[18] 劉甲斐，仇學(xué)梅.黑色素及其相關(guān)基因的研究進(jìn)展[J].生物技術(shù)通報(bào)，2007,4:55-58.

[19] Lam Do Phuong Uyen, Dung Hoang Nguyen, Eun-Ki Kim. Mechanism of skin pigmentation[J].Biotechnology and Bioprocess Engineering,2008,13:383-395.

[20] 沈海燕，張余光，楊軍.黑素小體轉(zhuǎn)運(yùn)與色素性病相關(guān)的研究進(jìn)展[J].中國(guó)美容醫(yī)學(xué)，2007,16(2)：272-275.

[21]Yamaguchi Yuji,Hearing V J.Melanocyte Distribution and Function in Human Skin[M].from Melanocytes to Melanoma,2006:101-115.

[22]Seiberg M. Keratinocy-melanocyte interactions during melanosome transfer[J].Pigment Cell Res,2001,14(4):236-242.

[23]Karolien Van Den Bossche,Naeyaert J M,Lambert J.The quest for the mechanism of melanin transfer[J].Traffic,2006,7:769-778.

[24]R?nnstrand L. Signal transduction via the stem cell factor receptor/c-Kit[J].Cellular and Molecular Life Sciences,2004,61:2535-2548.

[25] Hirota S,Isozaki K,Moriyama Y,etal.Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors[J].Science,1998,279(5350):577-580.

[26]Giebel L B,Spritz R A. Mutation of the KIT (mast/stem cell growth factor receptor) protooncogene in human piebaldism[J].Proc Natl Acad Sci USA,1991,88(19):8696-8699.

[27]楊井，涂亞庭，黃長(zhǎng)征.c-kit蛋白在惡心黑素瘤中的表達(dá)[J].中國(guó)皮膚性病學(xué)雜志，2004,18(9)：520-522.

[28]Mackenzie M A,Jordan S A,Budd P S,etal.Activation of the receptor tyrosine kinase Kit is required for the proliferation of melanoblast in the mouse embryo[J].Development Biology,1997,192:99-107.

[29]Geissler E N,Ryan M A,Housman D E.The dominant white spotting (W) locus of the mouse encodes the c-kit proto-oncogene[J].Cell,1988,55:185-192.

[30]Chabot B,Stephenson D A,Chapman V M,etal.The proto-oncogene c-kit encoding a transmembrane tyrosine kinase receptor maps to the mouse W locus[J].Nature,1988,335:88-89.

[31]Fontanesi L,Alessandro E D,Scotti E,etal.Genetic heterogeneity and selection signature at the KIT gene in pigs showing different coat colours and patterns[J].Animal Genetics,2010,41(5):478-492.

[32]Giuffra E,Evans G,T?rnsten A,etal.The Belt mutation in pigs is an allele at the Dominant white (I/KIT) locus[J].Mammalian Genome,1999,10:1132-1136.

[33]Moller M J,Chaudhary R,Hellmén E,etal.Pigs with the dominant white coat color phenotype carry a duplication of the of the KIT gene encoding the mast/stem cell growth factor receptor[J]. Mammalian Genome,1996,7:822-830.

[34]Naohiko OKUMURA, Toshimi MATSUMOTO, Noriyuki HAMASIMA,etal.Single nucleotide polymorphisms of the KIT and KITLG genes in pig[J].Animal Science Journal:2008,79:303-313.

[35]In Cheol Cho, Tao Zhong, Bo Young Seo,etal. Whole-genome association study for the roan coat color in an intercrossed pig population between Landrace and Korean native pig[J].Gene and Genomics,2011,33:17-23.

[36]Marklund S, Moller M, Sandberg K,etal. Close association between sequence polymorphism in the KIT gene and the roan coat color in horses[J].Mammalian Genome,1999,10:283-288.

[37]Brooks S A,Bailey E.Exon skipping in the KIT gene causes a Sabino spotting pattern in horses[J]. Mammalian Genome,2005,16:893-902.

[38]Haase B,Brooks S A,Tozaki T,etal.Seven novel KIT mutation in horse with white coat colour phenotypes[J].Animal Genetics,2009,40:623-629.

[39]Haase B, Heidi S H, Matthew M B,etal. Accumulating Mutations in Series of Haplotypes at the KIT and MITF Loci Are Major Determinants of White Markings in Franches-Montagnes Horses[J].Plos One,2013,8(9):e75071.

[40]Hume A N,Tarafder A K,Ramalho J S,etal.A coiled-coil domain of melanophilin is essential for Myosin Va recruitment and melanosome transport in melanocytes[J].Molecular Biology of the Cell,2006,17:4720-4735.

[41]Vaez M,Follett S A,Bed′hom B,etal.A single point-mutation within the melanophilin gene causes the lavender plumage colour dilution phenotype in the chicken[J].BMC Genetics,2008,9:7.

[42]Bed′hom B,Vaez M,Coville J L,etal.The lavender plumage colour in Japanese quailis associated with a complex mutation in the region of MLPH that is related to differences in growth, feed consumption and body temperature[J].BMC Genomics,2012,13:442.

[43]Philipp U,Hamann H,Mecklenburg L,etal.Polymorphisms within the canine MLPH gene are associated with dilute coat color in dogs[J]. BMC Genetics,2005,6:34.

[44]Dr?gemüller C,Philipp U,Haase B,etal.A noncoding melanophilin gene (MLPH) SNP at the splice donor of exon 1 represents a candidate causal mutation for coat color dilution in dogs[J].Journal of Heredity,2007,98(5):468-473.

[45]Ishida Y,David V A,Eizirik E,etal.A homozygous single-base deletion in MLPH causes the dilute coat color phenotype in the domestic cat[J].Genomics,2006,88:698-705.

[46]Lehner S,G?hle M,Dierks C,etal.Two-Exon Skipping within MLPH Is Associated with Coat Color Dilution in Rabbits[J].Plos One,2013,8(12):e84525.

[47]Cirera S,Markakis M N,Christensen K,etal.New insights into the melanophilin (MLPH) gene controlling coat color phenotypes in American mink[J].Gene,2013,527,48-54.

Research Progress of the Genes KIT and MLPH for Melanin Pigmentation in Animals

LIU Jie1,2LIU Yi2HU-YAN Jing-ke1HE Da-qian2LIU An-fang1

(1.SouthwestUniversity(RongchangCampus),Rongchang,Chongqing402460,China；2.ShanghaiAcademyofAgriculturalSciences,Shanghai201106,China)

The various skin colors and coat colors in animals are related to the type and amount of melanins deposited within the melanosomes. There are many genes participating in melanin deposition, involving KIT, MLPH and others. KIT and MLPH genes play important roles in melanogenesis and melanosome transfer, respectively. Previous studies have shown that mutations of KIT lead to phenotype changes in coat color of animals, while mutations of KIT are associated with human diseases. Variations of MLPH influence the coat colors in animals, resulting in dilution of coat color pigmentation. This paper presents an overview of melanocyte growth and development, melanin biosynthesis and transfer, and the research progress in KIT and MLPH genes in order that it may serve as important references for the study of the mechanisms of melanin deposition and skin, hair and plumage coloration.

KIT gene； MLPH gene； melanin； melanosome

*資助項(xiàng)目：國(guó)家現(xiàn)代農(nóng)業(yè)產(chǎn)業(yè)技術(shù)體系項(xiàng)目(CARS-43-4)。

劉 杰(1991-)，女，碩士，動(dòng)物遺傳育種與繁殖，E-mail：shangluoxi@163.com

劉安芳(1967-)，女，副教授，博士，主要從事家禽遺傳育種研究，E-mail：anfangliu@126.com