生物谷報(bào)道：盡管小鼠的色覺(jué)功能類(lèi)似于人類(lèi)紅綠色盲患者，這正如其它大多數(shù)哺乳動(dòng)物一樣,，科學(xué)家們已經(jīng)通過(guò)向小鼠染色體內(nèi)轉(zhuǎn)入一個(gè)人類(lèi)基因改變了它們的視覺(jué),。這個(gè)正常小鼠所不具備的人類(lèi)基因編碼一種光感受器，而將這一基因插入小鼠的染色體使其能夠辨別前所未有的顏色,。
在2007年3月23日發(fā)表在《科學(xué)》雜志上的一篇研究論文中,，來(lái)自約翰.霍普金斯大學(xué)Howard Hughes醫(yī)學(xué)中心的研究者同圣巴巴拉加利福尼亞大學(xué)的研究者一道通過(guò)一系列設(shè)計(jì)巧妙的色覺(jué)檢查，證實(shí)了通過(guò)基因調(diào)控可以使小鼠能夠分辨很廣泛的色譜,。這些實(shí)驗(yàn)是為了驗(yàn)證經(jīng)過(guò)基因治療的小鼠的大腦能否有效的感知它們眼內(nèi)的新的光感受器的信息,。在哺乳動(dòng)物中，只有靈長(zhǎng)類(lèi)動(dòng)物曾被發(fā)現(xiàn)具有如此精密的色覺(jué),，因此小鼠的大腦不需進(jìn)化就可以辨別這些色覺(jué)了,。包括小鼠在內(nèi)的大多數(shù)哺乳動(dòng)物都是二色視，它們只有S和M視錐細(xì)胞色素,。因此,，它們只能分辨人類(lèi)所能分辨顏色的一部分,。來(lái)自劍橋大學(xué)的John Mollon認(rèn)為三色視的進(jìn)化使靈長(zhǎng)類(lèi)動(dòng)物能夠分辨不成熟的和成熟的水果，前者以綠色為特征,，而后者為紅色和桔黃色,。與此相應(yīng)，成熟果實(shí)的顏色也與靈長(zhǎng)類(lèi)動(dòng)物的三色視一起進(jìn)化了,，因?yàn)槟切┳R(shí)別并且食用成熟果實(shí)的動(dòng)物通過(guò)傳播它們的種子而幫助了植物的繁殖,。
Gerald Jacobs 和Jeremy Nathans是本項(xiàng)研究的主要作者，他們說(shuō)：經(jīng)過(guò)基因工程改造的小鼠獲得新的色覺(jué)能力這一現(xiàn)象提示哺乳動(dòng)物的大腦具有可塑性,，使得其在復(fù)雜色覺(jué)方面具有幾乎同時(shí)升級(jí)的能力,。
色覺(jué)進(jìn)化是近三十多年來(lái)廣泛研究的課題。這一新的研究仍將是引導(dǎo)我們揭開(kāi)三色視之謎的最可靠的成果,，三色視是包括人類(lèi)在內(nèi)的靈長(zhǎng)類(lèi)動(dòng)物中存在的不同色覺(jué)功能,。三色視的基礎(chǔ)是視網(wǎng)膜上存在三種不同的感光細(xì)胞，能夠選擇性吸收不同波長(zhǎng)的光線刺激,，這就是我們所知道的視錐細(xì)胞,，每種視錐細(xì)胞含有一種吸收特定光線的感光蛋白。短波敏感視錐細(xì)胞（S細(xì)胞）對(duì)藍(lán)光最敏感,，中波敏感視錐細(xì)胞（M細(xì)胞）對(duì)綠光最敏感，而長(zhǎng)波敏感視錐細(xì)胞（L細(xì)胞）對(duì)紅光最敏感,。當(dāng)光線照射到視網(wǎng)膜而刺激視錐細(xì)胞時(shí),，大腦會(huì)比較S、M和L感光細(xì)胞的反應(yīng),，是大腦對(duì)其信號(hào)的綜合評(píng)價(jià)讓我們感受到不同的顏色,。
Nathans說(shuō)“我們今天在這些小鼠中看到的是具有革命性意義的事件，正如同發(fā)生在某位很久遠(yuǎn)的靈長(zhǎng)類(lèi)共同祖先身上的改變一樣,，這種改變最終使我們今天具有三色視色覺(jué),。”
在本項(xiàng)研究中，研究者試圖復(fù)制被大多數(shù)科學(xué)家認(rèn)可的靈長(zhǎng)類(lèi)動(dòng)物向三色視進(jìn)化的關(guān)鍵步驟：獲得L光感受器蛋白,。Jacobs解釋說(shuō)：研究目的是確定單純轉(zhuǎn)入這一基因能否改變動(dòng)物的感光功能,。因?yàn)檫€不確定單純的增加這一基因是否足夠產(chǎn)生色覺(jué)的改變，或者需要增加神經(jīng)系統(tǒng)的改變,？
據(jù)研究者稱(chēng),，他們的發(fā)現(xiàn)并不僅僅適用于視覺(jué)的進(jìn)化，而且適用于一般的感覺(jué)系統(tǒng)的進(jìn)化過(guò)程,。此前的關(guān)于視覺(jué),、嗅覺(jué)（聞）以及味覺(jué)（嘗）系統(tǒng)的研究提示轉(zhuǎn)入一個(gè)新的感覺(jué)感受器可以增加動(dòng)物的感覺(jué)范圍，改變它的行為和神經(jīng)活動(dòng),。Jacobs提示說(shuō)本次新的研究是首次證明基因的簡(jiǎn)單改變可以帶來(lái)巨大的效應(yīng),。如果神經(jīng)系統(tǒng)具有正如我們已經(jīng)在小鼠中發(fā)現(xiàn)的可塑性,，我們通過(guò)簡(jiǎn)單改變感受器蛋白，不但可以改變動(dòng)物所能感受信息的范圍,，而且可以得出新的經(jīng)驗(yàn),。
作者在《科學(xué)》雜志的論文中寫(xiě)到：“我們觀察到的小鼠大腦能夠利用感光信息分辨顏色的現(xiàn)象提示：感受器基因的改變也許具有直接的選擇效應(yīng)，不但是因?yàn)檫@能擴(kuò)大可感知的刺激的范圍或種類(lèi),，而且是因?yàn)檫@使得具有可塑性的神經(jīng)系統(tǒng)可以分辨新的和已經(jīng)存在的刺激,。隨后的更多基因改變使得神經(jīng)通路更有效地獲取感覺(jué)信息，但這可能需要許多代的進(jìn)化來(lái)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.
原文出處：
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 »|
作者簡(jiǎn)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.
