Genetic Enhancements Make Mice See Red
BALTIMORE, Md., March 23, 2007 -- Researchers have transformed the limited color vision of mice by introducing a single human gene into a mouse chromosome. The gene codes for a light sensor that mice do not normally possess, and its insertion allowed the mice to see colors as never before, a sign that the brain can adapt far more rapidly to new sensory information than anticipated.
The work, by scientists at the Johns Hopkins School of Medicine and their colleagues, also suggests that when the first ancestral primate inherited a new type of photoreceptor more than 40 million years ago, it probably experienced immediate color enhancement, which may have allowed the trait to spread quickly.
In research conducted by scientists at the Johns Hopkins School of Medicine, colored lights were used to show that the brains of genetically altered mice could efficiently process sensory information from new photoreceptors in their eyes. Here, a mouse deciding that the third colored panel looks different from the other two receives a drop of soy milk as a reward. For this set of three lights, only the soy milk dispenser over the third panel releases a drop of milk. (Photo: Gerald Jacobs)
"If you gave mice a new sensory input at the front end, could their brains learn to make use of the extra data at the back end?" asked Dr. Jeremy Nathans, professor of molecular biology and genetics, neuroscience and ophthalmology at Johns Hopkins. "The answer is, remarkably, yes. They did not require additional generations to evolve new sight."
Retinas of primates such as humans and monkeys are unique among mammals in that they have three visual receptors that absorb short (blue), medium (green) and long (red) wavelengths of light. Mice, like other mammals, only have two; one for short and one for medium wavelengths.
In the study, the researchers designed a "knock-in" mouse that has one copy of its medium wavelength receptor replaced with the human long wavelength receptor, so both were expressed in the retina. The human receptors were biologically functional in the mice, but the real question was whether the mice could use the new visual information.
To address this question, the researchers used a classic preference test; mice set before three light panels were trained to touch the one panel that appeared to differ from the other two. A correct answer was rewarded with a drop of soy milk.
To circumvent thorny issues related to the subjective nature of color perception -- everyone who has had a discussion as to whether the "green" they see is the same as the "green" their friend sees can attest to this -- the researchers only tested whether the mice could discriminate among the lights.
In humans, color vision is dependent on three types of photoreceptor cells in the retina. Short-wavelength-sensitive (S) cone cells are most sensitive to blue lights, medium-wavelength-sensitive (M) cone cells are most sensitive to green lights, and long-wavelength-sensitive (L) cones are most sensitive to red lights. Most mammals, including mice, possess only S and M cone pigments and can distinguish only a fraction of the wavelengths that can be distinguished by humans. The two spectra shown illustrate researchers' best guess as to how mice—normal mice and those that have been genetically modified to express long-wavelength-sensitive cone cells—perceive light of different wavelengths. (Illustration: Jim Holloway)
"Each photoreceptor absorbs a range of wavelengths, but the efficiency changes with wavelength," Nathans said. "For example, one photoreceptor might absorb green light only half as efficiently as red light. If an animal had only this type of photoreceptor, then a green light that was twice as bright as a red light would look identical to the red one. But if the animal adds a second photoreceptor with different absorption properties, then by comparing both receptors, the red and green lights could always be distinguished."
Normal mice failed to discriminate yellow versus red lights when the light intensities were set to give equal activation of their middle wavelength receptor. However, mice with both the human long wavelength and the mouse middle wavelength receptors learned to tell the difference, although it took over 10,000 trials to learn to make the distinction.
Nathans suggests that these knock-in mice mimic how our earliest primate ancestors acquired trichromatic vision, color vision based on three receptors. At some point in the past, random mutations created a variant of one receptor gene, located on the X chromosome, producing two different receptor types. Present-day New World (South American) monkeys still use this system, which means that in these monkeys only certain females can acquire trichromatic color vision.
In contrast, among Old World (African) primates such as humans, the two different X chromosome genes duplicated so that each X chromosome now carries the genes for both receptor types, giving both males and females trichromatic color vision.
"You could say that the original primate color vision system, and the one that New World monkeys still use today, is the poor man's -- or to be accurate, poor woman's -- version of color vision," Nathans said.
The research was funded by the National Eye Institute and the Howard Hughes Medical Institute. It appears in the March 23 issue of Science; authors on the paper are Jeremy Nathans and Hugh Cahill of Johns Hopkins, and Gerald Jacobs and Gary Williams of the University of California, Santa Barbara.
For more information, visit: www.hhmi.org/news/nathans20070323.html
- The attribute of visual experience that can be described as having quantitatively specifiable dimensions of hue, saturation, and brightness or lightness. The visual experience, not including aspects of extent (e.g., size, shape, texture, etc.) and duration (e.g., movement, flicker, etc.).
- The technology of generating and harnessing light and other forms of radiant energy whose quantum unit is the photon. The science includes light emission, transmission, deflection, amplification and detection by optical components and instruments, lasers and other light sources, fiber optics, electro-optical instrumentation, related hardware and electronics, and sophisticated systems. The range of applications of photonics extends from energy generation to detection to communications and...
- The processes in which luminous energy incident on the eye is perceived and evaluated.
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