生物谷报道：尽管小鼠的色觉功能类似于人类红绿色盲患者，这正如其它大多数哺乳动物一样，科学家们已经通过向小鼠染色体内转入一个人类基因改变了它们的视觉。这个正常小鼠所不具备的人类基因编码一种光感受器，而将这一基因插入小鼠的染色体使其能够辨别前所未有的颜色。
在2007年3月23日发表在《科学》杂志上的一篇研究论文中，来自约翰.霍普金斯大学Howard Hughes医学中心的研究者同圣巴巴拉加利福尼亚大学的研究者一道通过一系列设计巧妙的色觉检查，证实了通过基因调控可以使小鼠能够分辨很广泛的色谱。这些实验是为了验证经过基因治疗的小鼠的大脑能否有效的感知它们眼内的新的光感受器的信息。在哺乳动物中，只有灵长类动物曾被发现具有如此精密的色觉，因此小鼠的大脑不需进化就可以辨别这些色觉了。包括小鼠在内的大多数哺乳动物都是二色视，它们只有S和M视锥细胞色素。因此，它们只能分辨人类所能分辨颜色的一部分。来自剑桥大学的John Mollon认为三色视的进化使灵长类动物能够分辨不成熟的和成熟的水果，前者以绿色为特征，而后者为红色和桔黄色。与此相应，成熟果实的颜色也与灵长类动物的三色视一起进化了，因为那些识别并且食用成熟果实的动物通过传播它们的种子而帮助了植物的繁殖。
Gerald Jacobs 和Jeremy Nathans是本项研究的主要作者，他们说：经过基因工程改造的小鼠获得新的色觉能力这一现象提示哺乳动物的大脑具有可塑性，使得其在复杂色觉方面具有几乎同时升级的能力。
色觉进化是近三十多年来广泛研究的课题。这一新的研究仍将是引导我们揭开三色视之谜的最可靠的成果，三色视是包括人类在内的灵长类动物中存在的不同色觉功能。三色视的基础是视网膜上存在三种不同的感光细胞，能够选择性吸收不同波长的光线刺激，这就是我们所知道的视锥细胞，每种视锥细胞含有一种吸收特定光线的感光蛋白。短波敏感视锥细胞（S细胞）对蓝光最敏感，中波敏感视锥细胞（M细胞）对绿光最敏感，而长波敏感视锥细胞（L细胞）对红光最敏感。当光线照射到视网膜而刺激视锥细胞时，大脑会比较S、M和L感光细胞的反应，是大脑对其信号的综合评价让我们感受到不同的颜色。
Nathans说“我们今天在这些小鼠中看到的是具有革命性意义的事件，正如同发生在某位很久远的灵长类共同祖先身上的改变一样，这种改变最终使我们今天具有三色视色觉。”
在本项研究中，研究者试图复制被大多数科学家认可的灵长类动物向三色视进化的关键步骤：获得L光感受器蛋白。Jacobs解释说：研究目的是确定单纯转入这一基因能否改变动物的感光功能。因为还不确定单纯的增加这一基因是否足够产生色觉的改变，或者需要增加神经系统的改变？
据研究者称，他们的发现并不仅仅适用于视觉的进化，而且适用于一般的感觉系统的进化过程。此前的关于视觉、嗅觉（闻）以及味觉（尝）系统的研究提示转入一个新的感觉感受器可以增加动物的感觉范围，改变它的行为和神经活动。Jacobs提示说本次新的研究是首次证明基因的简单改变可以带来巨大的效应。如果神经系统具有正如我们已经在小鼠中发现的可塑性，我们通过简单改变感受器蛋白，不但可以改变动物所能感受信息的范围，而且可以得出新的经验。
作者在《科学》杂志的论文中写到：“我们观察到的小鼠大脑能够利用感光信息分辨颜色的现象提示：感受器基因的改变也许具有直接的选择效应，不但是因为这能扩大可感知的刺激的范围或种类，而且是因为这使得具有可塑性的神经系统可以分辨新的和已经存在的刺激。随后的更多基因改变使得神经通路更有效地获取感觉信息，但这可能需要许多代的进化来完成。”
Fig. 1. (A) ERG spectral sensitivity for mice expressing the M pigment. Data points are mean values for 12 animals. The curve is that for the best-fitting photopigment absorption function. (B) Mean spectral sensitivity function for 18 mice expressing the human L pigment. (C) Spectral sensitivity for 82 heterozygous mice. The curve is the best-fit linear summation of curves derived from those in (A) and (B). (D) Distribution of the L:M cone weightings required to best fit each of the heterozygous mice represented in (C). (E) Mean V-log I functions obtained from activation of either mouse M or human L pigments. Light intensity has been specified according to its calculated effectiveness on each of these pigments. sec, seconds; sr, steradians. For derivation of the fitted functions, see SOM. (F) Increment-threshold measurements. The inset schematizes the discrimination context in which, on each trial, a monochromatic test light was added to any oneofthe threepanels, allofwhich were steadily illuminated with identical achromatic light. The colored bars depict the difference in the thresholds obtained for 500- and 600-nm test lights for mice whose retinas contained either mouse M (n = 4 mice) or both M and L (n = 7 mice) pigments. Error bars in [(A) to (C)] and [(E) and (F)] indicate 2 SDs.
原文出处：
Science 23 March 2007 Vol 315, Issue 5819
Emergence of Novel Color Vision in Mice Engineered to Express a Human Cone Photopigment
Gerald H. Jacobs, Gary A. Williams, Hugh Cahill, and Jeremy Nathans
Science 23 March 2007: 1723-1725.
Mice engineered to express the human long-wavelength opsin in addition to its own two color vision pigments acquire a new ability to distinguish colors.
Abstract »| Full Text »| PDF »| Supporting Online Material »|
作者简介：
Gerald H. Jacobs
Research Professor, Psychology
Current Research Selected Publications Contact Information
Gerald Jacobs received a B.A. degree at University of Vermont and a Ph. D. from Indiana University. After serving for five years on the faculty of the University of Texas, Austin he came to UCSB in 1969. Professor Jacobs is a member of the Neuroscience Research Institute at UCSB. He has authored more than 200 journal papers and chapters on a wide range of topics dealing with vision and the visual system. Jacobs is a fellow of the Optical Society of America and of the American Association for the Advancement of Science. Among his major professional honors are the Rank Prize in Optoelectronics (1986), Faculty Research Lecturer of the University of California, Santa Barbara (1996), and the Proctor Medal of the Association for Research in Vision and Ophthalmology (1998).
Jeremy Nathans, M.D., Ph.D
Professor of Molecular Biology and Genetics
Department of Molecular Biology and Genetics Johns Hopkins University School of Medicine
School of Medicine
Molecular Biology of Vision and Pattern Formation in Development
The principal research interests of the Nathans lab center on two areas: (1) the structure and function of the vertebrate visual system and (2) the origins of pattern formation in development.
The Nathans laboratory is approaching questions related to the visual system by studying the retina. The questions we are asking are: (1) How are the patterns of cell identity in the retina determined at a molecular level? (2) How is the final performance of the system affected by individual molecules and molecular events? (3) How is the remarkable structure of photoreceptor cells generated? (4) What are the pathologic mechanisms responsible for blinding diseases and how can this knowledge be applied to therapeutic intervention?
Research in the Nathans laboratory on pattern formation focuses on the mechanism of action and biological role of a large family of transmembrane receptors referred to as "Frizzled" proteins, a name that reflects the odd appearance of those Drosophila in which one of the Frizzled genes is mutated. The Frizzled proteins act as receptors for a family of secreted signaling proteins referred to as Wnts, but at least one non-Wnt ligand activates one of the Frizzleds. Using knock-out mice, we have shown that a remarkably diverse group of developmental processes relies on Frizzled action, including blood vessel development in the retina, development of the cerebellum, axonal growth and path finding in the spinal cord and forebrain, and hair patterning on the body surface. We are currently investigating the mechanisms underlying Frizzled action in these various contexts, and searching for additional roles of Frizzled proteins.
In both areas of research, the Nathans laboratory uses genetically engineered mice, cell culture approaches, in vitro biochemical experiments with purified proteins, and the analysis of genes and proteins responsible for inherited human diseases.
