Scientists Genetically Engineer Mice with Better Vision

Johns Hopkins and University of California Santa Barbara researchers demonstrated enhancement of vision in mice by introducing a human gene that codes for the receptor on long-wavelength-sensitive (L) cones of the human retina. Mice normally possess short-wavelength-sensitive (S) and medium-wavelength-sensitive (M) cone cells. Hence their vision is skewed away from the red spectrum.
From a statement by the Howard Hughes Medical Institute:

Most mammals, including mice, are dichromats, possessing only S and M cone pigments. As a consequence, they can distinguish only a fraction of the wavelengths that can be distinguished by humans. John Mollon at the University of Cambridge has suggested that the evolution of trichromacy could have permitted primates to discriminate between unripe fruit, which is typically green, and ripe red- and orange-colored fruits. Reciprocally, the colors of ripened fruits may have coevolved with primate trichromacy, since animals that could recognize and eat the ripe fruit would have assisted plants by spreading their seeds…
In the current study, the researchers set out to replicate what most scientists had considered the crucial step in the evolution of trichromactic color vision in primates: the introduction of the L receptor gene. Their goal was to determine whether that gene alone could alter an animal’s sensory perception. “It’s been unclear,” Jacobs explained, “whether the simple addition of a photopigment is sufficient to yield a new dimension of color vision, or whether you might need, in addition, some changes in the nervous system.”
In 2003, Nathans and Jacobs, together with Markus Meister at Harvard University, reported their initial studies on genetically engineered mice carrying the L receptor gene in place of the M receptor gene. Because these genes are carried on the X-chromosome, they are subject to a process known as X-chromosome inactivation. In mammals, every cell in females has two X-chromosomes, while every cell in males has a single X-chromosome. X-inactivation occurs only in females and results in the silencing of most of the genes on one of the X-chromosomes in each cell. Because different cells choose to silence either one or the other of the X-chromosomes, female mice engineered to have one copy each of the M and L receptor genes express the M receptor in some cone cells and the L receptor in other cone cells. These two different types of cones are intermingled with one another across the surface of the retina. This X-inactivation-based mechanism for producing M and L receptors in different cone cells is the same as the one that Jacobs had identified earlier in New World primates. For the current study, the team selected mice that possessed roughly equal ratios of M and L cone cells, and compared their vision to that of normal mice.
Jacobs’ group at UCSB developed behavioral tests to determine whether the female mice could discriminate among colored lights by comparing the relative activation of the M and L cone cells. The researchers conducted tens of thousands of tests in which two different wavelengths or intensities of light were displayed on three test panels. Mice received a drop of soymilk as a reward when they correctly identified which panel differed from the other two. The genetically altered mice demonstrated their new visual ability by choosing the correct panel in 80 percent of the trials. By contrast, normal mice only chose correctly one third of the time, the score that one would obtain by guessing randomly among the three panels.
According to the scientists, their findings have implications not just for the evolution of color vision, but for the evolution of sensory systems in general. Previous experiments with the visual, olfactory (smell), and gustatory (taste) systems have suggested that introducing a new sensory receptor can expand the range of an animal’s sensory perception, altering both its behavior and nerve activity, Jacobs noted that the new study is the first to demonstrate that these simple genetic changes can have even more profound effects. “By simply changing receptor proteins, not only can you extend the range of information that an animal might be able to sense, but if the nervous system has the plasticity we’ve seen in these mice, you can extract a new dimension of experience,” he explained.
“Our observation that the mouse brain can use this information to make spectral discriminations implies that alterations in receptor genes might be of immediate selective value not only because they expand the range or types of stimuli that can be detected but also because they permit a plastic nervous system to discriminate between new and existing stimuli,” the authors wrote in the Science paper. “Additional genetic changes that refine the downstream neural circuitry to more efficiently extract sensory information could then follow over many generations.”

Howard Hughes Medical Institute: Genetic Studies Endow Mice with New Color Vision…