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Making mice with enhanced color vision
March 23, 2007Researchers at the Johns Hopkins School of Medicine and their colleagues have found that mice simply expressing a human light receptor in addition to their own can acquire new color vision, a sign that the brain can adapt far more rapidly to new sensory information than anticipated.
This work, appearing March 23 in Science, 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 this trait to spread quickly.
"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?" asks Jeremy Nathans M.D., Ph.D., professor of molecular biology and genetics, neuroscience, and ophthalmology at 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.
"Each photoreceptor absorbs a range of wavelengths, but the efficiency changes with wavelength," Nathans explains. "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 says.
Johns Hopkins Medical Institutions
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.
"Each photoreceptor absorbs a range of wavelengths, but the efficiency changes with wavelength," Nathans explains. "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 says.
Johns Hopkins Medical Institutions
Color Vision News and Current Color Vision Events RSSNYU Researchers id new class of photoreceptors,pointing to new ways sights-and smells-are regulated
The identification of a new class of photoreceptors in the retina of fruit flies sheds light on the regulation of the pigments of the eye that confer color vision, researchers at New York University's Center for Developmental Genetics report in a new study appearing in the Public Library of Science's journal, PloS Biology.
NYU scientists set stage for understanding how color vision is processed
New York University biologists have mapped the medulla circuitry in fruit flies, setting the stage for subsequent research on how color vision is processed.
Scientists find color vision system independent of motion detection
The vision system used to process color is separate from that used to detect motion, according to a new study by researchers at New York University's Center for Developmental Genetics and in the Department of Genetics and Neurobiology at Germany's University of Würzburg.
New study uncovers secrets behind butterfly wing patterns
The genes that make a fruit fly's eyes red also produce red wing patterns in the Heliconius butterfly found in South and Central America, finds a new study by a UC Irvine entomologist.
The aye-ayes have it: The preservation of color vision in a creature of the night
A quest to gain a more complete picture of color vision evolution has led Biodesign Institute researcher Brian Verrelli to an up-close, genetic encounter with one of the world's most rare and bizarre-looking primates.
Which came first: Primates' ability to see colorful food or see colorful sex?
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Color Vision Drove Primates to Develop Red Skin and Hair, Study Finds
You might call it a tale of "monkey see, monkey do." Researchers at Ohio University have found that after primates evolved the ability to see red, they began to develop red and orange skin and hair.
UF researchers awaken vision cells in blind mice
University of Florida researchers used gene therapy to restore sight in mice with a form of hereditary blindness, a finding that has bearing on many of the most common blinding diseases.
Study offers window into human behavior, brain disease
UCSF scientists have identified a cell population that is a primary target of the degenerative brain disease known as frontotemporal dementia, which is as common as Alzheimer's disease in patients who develop dementia before age 65.
Pioneers in field of functional genomics work toward gene therapy for vision defects
"Primates and humans have three photoreceptors and can only see four basic colors, red, green, blue and yellow," says Jay Neitz, Ph.D. "Birds, fish and reptiles have four photoreceptors, allowing them to see things we cannot. They must see an entire dimension of color, including ultraviolet, infrared and all the combinations thereof, which we miss."
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