Development of a novel pink-eyed dilution mouse model showing progressive darkening of the eyes and coat hair with aging.
Development of a novel pink-eyed dilution mouse model showing progressive darkening of the eyes and coat hair with aging.
复制标题
开发一种新型的粉红色稀释小鼠模型，显示了眼睛的渐进性变黑，并与衰老涂上头发。
DOI：
10.1538/expanim.14-0101
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发表时间：
2015
影响因子：
2.4
通讯作者：
Yamagishi Y
中科院分区：
文献类型：
--
作者：
Ishikawa A;Sugiyama M;Hondo E;Kinoshita K;Yamagishi Y
Oca2p-cas(眼皮肤白化病II；粉眼稀释性卡氏小鼠)是小鼠7号染色体上的一个毛色突变基因，在野生卡氏小鼠中自发产生。Oca2p-cas纯合子小鼠在非刺鼠遗传背景下通常表现为粉红色的眼睛和灰色的毛发，并且这种普通的表型在一生中保持不变。在C57BL/6J背景上培育携带该基因的混合菌株的过程中，我们发现了一种新的自发突变，该突变会导致眼睛和毛发随着年龄的增长而变黑。在这项研究中，我们开发了一种新的小鼠模型，显示了这种独特的表型。大体观察显示，新突变的幼鼠出生后大约3个月，粉色眼睛和灰色毛发逐渐变暗。光镜和透射电子显微镜观察显示，与普通小鼠相比，新小鼠的毛发干和眼睛脉络膜的黑色素沉着显着增加。Oca2p-cas的序列分析显示，其野生型基因外显子15和16存在4.1kb的缺失。然而，这两种类型的突变小鼠之间没有序列差异。交配实验表明，由于不完全外显，新的突变体表型不是以简单的方式遗传的。这种新的自发突变小鼠是进行性毛发变黑动物的第一个例子，也是理解黑色素生物合成随年龄增长的调节机制的基本动物模型。
Oca2p-cas (oculocutaneous albinism II; pink-eyed dilution castaneus) is a coat color mutant gene on mouse chromosome 7 that arose spontaneously in wild Mus musculus castaneus mice. Mice homozygous for Oca2p-cas usually exhibit pink eyes and gray coat hair on the non-agouti genetic background, and this ordinary phenotype remains unchanged throughout life. During breeding of a mixed strain carrying this gene on the C57BL/6J background, we discovered a novel spontaneous mutation that causes darkening of the eyes and coat hair with aging. In this study, we developed a novel mouse model showing this unique phenotype. Gross observations revealed that the pink eyes and gray coat hair of the novel mutant young mice became progressively darker in color by approximately 3 months after birth. Light and transmission-electron microscopic observations revealed a marked increase in melanin pigmentation of coat hair shafts and choroid of the eye in the novel mice compared to that in the ordinary mice. Sequence analysis of Oca2p-cas revealed a 4.1-kb deletion involving exons 15 and 16 of its wild-type gene. However, there was no sequence difference between the two types of mutant mice. Mating experiments suggested that the novel mutant phenotype was not inherited in a simple fashion, due to incomplete penetrance. The novel spontaneous mutant mouse is the first example of progressive hair darkening animals and is an essential animal model for understanding of the regulation mechanisms of melanin biosynthesis with aging.
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影响因子：
14.8
作者：
Kumar, Prateek;Henikoff, Steven;Ng, Pauline C.
通讯作者：
Ng, Pauline C.
影响因子：
4.3
作者：
Hirobe, Tomohisa;Ito, Shosuke;Wakamatsu, Kazumasa
通讯作者：
Wakamatsu, Kazumasa
影响因子：
56.9
作者：
Nishimura, EK;Granter, SR;Fisher, DE
通讯作者：
Fisher, DE
影响因子：
56.9
作者：
GARDNER, JM;NAKATSU, Y;BRILLIANT, MH
通讯作者：
BRILLIANT, MH
影响因子：
2.6
作者：
Ishikawa, Akira
通讯作者：
Ishikawa, Akira