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Fig. 6. Comparison of behavioral spectral sensitivity functions obtained from wild-type mice (triangles) and transgenic mice (solid circles) incorporating a functional human L-cone opsin gene. Note that the transgenic mice have significantly higher sensitivity to long-wavelength test lights. (Data derived from [62].)
pigment additions per se can yield immediate alterations in behavioral capacity, and such changes could provide an adaptive advantage.
The transgenic mouse just described features a retina that contains three types of cone pigment: native UV, native M, and human L. During evolution, the addition of a new pigment is frequently associated with the emergence of a new dimension of color vision. That capacity did not appear in this transgenic, likely because the transgene was incorporated onto an autosome; thus, human L and mouse M pigment became coexpressed in individual cones [62]. To better approximate the arrangement that normally occurs in mammals would require that the new opsin gene be X chromosome linked; genetically engineered knock-in mice that satisfy that criterion have been developed [63, 64]. In these animals, the normal mouse M-opsin gene (which is located on the X chromosome) was replaced with a construct incorporating the human L-opsin gene. With subsequent breeding, this yields three separate cone pigment phenotypes: All mice have a normal UV pigment with hemizygous males and homozygous females in addition to having either mouse M or human L pigment. At the same time, heterozygous females have both M and L pigments, and through the agency of random X-chromosome inactivation, these two pigments become separately expressed in mouse cones. As for the earlier developed transgenic mice, the novel pigment functions well in these knock-in mice and can be readily shown to support enhanced visual sensitivity. Recent experiments show that these mice can also acquire a new capacity for color vision [65]. These results dramatically demonstrate that adding components to the nervous system via genetic engineering can provide a useful new tool to study the organization of the visual system, thus allowing something close to actual laboratory studies of evolution.
MOUSE AND HUMAN CONE VISION
The general advantages of using mice as models for studies of human ocular disease and basic retinal biology have been well documented (e.g., [66]). These include the highly conserved features of the two genomes, the ability to control and manipulate
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mouse genetic backgrounds, and the general similarities of retinal construction across all mammals. Because humans are diurnal and because our species has uniquely developed the lighting technology that allows us to convert environmental conditions that would normally involve rod vision into photopic viewing, much of the interest in human vision and human visual pathology focuses on cones. In using mice as models for human cone vision, one has to be cognizant of species differences as well as their similarities. Some of these issues have been noted, and it may be useful to conclude this survey of conebased vision in the mouse by reminding of the following points of difference between mouse and human cone vision:
1.The foveal region of the human retina has a unique structural and functional organization that is unmatched by that found anywhere in the mouse retina.
2.Because of differences in cone pigment complement and preretinal filtering, mice have significant sensitivity to UV radiation that is absent from human vision. One practical consequence of this difference is that visual stimuli frequently used to test mice (e.g., computer monitors) fail to provide photic inputs that maximize the full range of mouse visual capacity.
3.Many mouse cones coexpress two classes of photopigment. This alters dramatically the prospects for deriving color vision and renders signal transmission in the visual system different from what it is in mammals like humans without receptor coexpression.
4.By comparative standards, the mouse has poor visual acuity. This makes it challenging to accurately document small differences in spatial resolution or gradual changes in spatial vision that may be engendered by disease, by age, or by environmental manipulations.
ACKNOWLEDGMENT
Preparation of this chapter was facilitated by a grant from the National Eye Institute (EY002052).
REFERENCES
1.Boursot, P., Din, W., Anand, R., Darviche, D., Dod, B., von Demling, F., Talwar, G. P., Bonhomme, P. (1996). Origin and radiation of the house mouse: Mitochondrial DNA phylogeny. J Evol Biol 9, 391–415.
2.Beck, J. A., Lloyd, S., Hafezparast, M., Lennon-Pierce, M., Eppig, M. T., Festing, M. F., Fisher, E. M. (2000). Genealogies of mouse inbred strains. Nat Genet 24, 23–25.
3.Jacobs, G. H. (1993). The distribution and nature of colour vision among the mammals. Biol Rev 68, 413–471.
4.Ahnelt, P. K., Kolb, H. (2000). The mammalian photoreceptor mosaic-adaptive design. Progr Retin Eye Res 19, 711–770.
5.Carter-Dawson, L. D., LaVail, M. M. (1979). Rods and cones in the mouse retina. I. Structural analysis using light and electron microscopy. J Comp Neurol 188, 245–262.
6.Blanks, J., Johnson, L. V. (1984). Specific binding of peanut lectin to a class of retinal photoreceptor cells: a species comparison. Invest Ophthal Vis Sci 25, 546–557.
7.Jeon, C.-J., Strettoi, E., Masland, R. H. (1998). The major cell populations of the mouse retina. J Neurosci 18, 8936–8946.
8.Williams, G. A., Daigle, K. A., Jacobs, G. H. (2005). Rod and cone function in coneless mice. Vis Neurosci 22, 807–816.
Mouse Cone Pigments and Vision |
371 |
9.Lukats, A., Szabo, A., Rohlich, P., Vigh, B., Szel, A. (2005). Photopigment coexpression in mammals: comparative and developmental aspects. Histol Histopathol 20, 551–574.
10.Curcio, C. A., Sloan, K. R., Kalina, R. E., Hendrickson, A. E. (1990). Human photoreceptor topography. J Comp Neurol 292, 497–523.
11.Schmucker, C., Schaeffel, F. (2004). A paraxial schematic eye model for the growing C57BL/6 mouse. Vision Res 44, 1857–1867.
12.Zhou, G., Williams, R. W. (1999). Mouse models for myopia: an analysis of variation in eye size in adult mice. Optom Vision Sci 76, 408–418.
13.Williams, R. W., Strom, R. C., Rice, D. S., Goldowitz, D. (1996). Genetic and environmental control of variation in retinal ganglion cell number in mice. J Neurosci 16, 7193–7205.
14.Jacobs, G. H. (1992). Ultraviolet vision in vertebrates. Am Zool 32, 544–554.
15.Jacobs, G. H., Neitz, J., Deegan II, J. F. (1991). Retinal receptors in rodents maximally sensitive to ultraviolet light. Nature 353, 655–656.
16.Peichl, L. (2005). Diversity of mammalian photoreceptor properties: adaptations to habitat and lifestyle? Anat Rec A 287A, 1001–1012.
17.Lyubarsky, A. L., Falsini, B., Pennesi, M. E., Valentini, P., Pugh, E. N., Jr. (1999). UVand midwave-sensitive cone-driven retinal responses of the mouse: a phenotype for coexpression of cone photopigments. J Neurosci 19, 442–455.
18.Yokoyama, S., Radlwimmer, F. B., Kawamura, S. (1998). Regeneration of ultraviolet pigments of vertebrates. FEBS Lett 423, 155–158.
19.Sun, H., Macke, J. P., Nathans, J. (1997). Mechanisms of spectral tuning in the mouse green cone pigment. Proc Natl Acad Sci U S A 94, 8860–8865.
20.Yokoyama, S. (2002). Molecular evolution of color vision in vertebrates. Gene 300, 69–78.
21.Hunt, D. M., Cowing, J. A., Wilkie, S. E., Parry, J. W. L., Poopalasundaram, S., Bowmaker,
J.K. (2004). Divergent mechanisms for the tuning of shortwave sensitive visual pigments in vertebrates. Photochem Photobiol Sci 3, 713–720.
22.Yokoyama, S., Radlwimmer, F. B. (1999). The molecular genetics of red and green color vision in mammals. Genetics 153, 919–932.
23.Shi, Y., Yokoyama, S. (2003). Molecular analysis of the evolutionary significance of ultraviolet vision in vertebrates. Proc Natl Acad Sci U S A 100, 8308–8333.
24.Szel, A., Rohlich, P., Caffe, A. R., Juliusson, B., Aguire, G., Van Veen, T. (1992). Unique separation of two spectral classes of cones in the mouse retina. J Comp Neurol 325, 327–342.
25.Calderone, J. B., Jacobs, G. H. (1995). Regional variations in the relative sensitivity to UV light in the mouse retina. Vis Neurosci 12, 463–468.
26.Applebury, M. L., Antoch, M. P., Baxter, L. C., Chun, L. L. Y., Falk, J. D., Farhangfar, F., Kage, K., Kryzystolik, M. L., Lyass, L. A., Robbins, J. T. (2000). The murine cone photoreceptor: a single cone type expresses both S and M opsins with retinal spatial patterning. Neuron 27, 513–523.
27.Haverkamp, S., Wassle, H., Duebel, J., Kuner, T., Augustine, G. J., Feng, G., Euler, T. (2005). The primordial, blue-cone color system of the mouse retina. J Neurosci 25, 5438–5445.
28.Nikonov, S. S., Kholodenko, R., Lem, J., Pugh, E. N., Jr. (2006). Physiological features of the S- and M-cone photoreceptors of wild-type mice from single cell recordings. J Gen Physiol 127, 359–374.
29.Wikler, K. C., Szel, A., Jacobsen, A.-L. (1996). Positional information and opsin identity in retinal cones. J Comp Neurol 374, 96–107.
30.Ng, L., Hurley, J. B., Dierks, B., Srinivas, M., Salto, C., Vennstrom, B., Reh, T. A., Forrest,
D.(2001). A thyroid hormone receptor that is required for the development of green cone photoreceptors. Nat Genet 27, 94–98.
372 |
Jacobs |
31.Roberts, M. R., Srinivas, M., Forrest, D., Morreale de Escobar, G., Reh, T. A. (2006). Making the gradient: thyroid hormone regulates cone opsin expression in the developing mouse retina. Proc Natl Acad Sci U S A 103, 6218–6223.
32.Srinivas, M., Ng, L., Liu, H., Jia, L., Forrest, D. (2006). Activation of the blue opsin gene in cone photoreceptor development by RORβ orphan nuclear receptor. Mol Endocrinol 20, 1728–1741.
33.Masland, R. H. (2001). The fundamental plan of the retina. Nat Neurosci 4, 877–886.
34.Wassle, H. (2004). Parallel processing in the mammalian retina. Nat Neurosci 19, 747–757.
35.Jacobs, G. H., Williams, G. A., Fenwick, J. A. (2004). Influence of cone pigment coexpression on spectral sensitivity and color vision in the mouse. Vision Res 44, 1615–1622.
36.Ekesten, B., Gouras, P., Yamamoto, S. (2000). Cone inputs to murine retinal ganglion cells. Vision Res 40, 2573–2577.
37.Ekesten, B., Gouras, P. (2005). Cone and rod inputs to murine retinal ganglion cells: evidence of cone opsin specific channels. Vis Neurosci 22, 893–903.
38.Pinto, L. H., Enroth-Cugell, C. (2000). Tests of the mouse visual system. Mammal Genom 14, 531–536.
39.Gianfranceschi, L., Fiorentini, A., Maffei, L. (1999). Behavioural visual acuity of wild type and bc12 transgenic mice. Vision Res 39, 569–574.
40.Hayes, J. M., Balkema, G. W. (1993). Elevated dark-adapted thresholds in hypopigmented mice measured with a water maze screen apparatus. Behav Genet 23, 395–403.
41.Prusky, G. T., West, P. W. R., Douglas, R. M. (2000). Behavioral assessment of visual acuity in mice and rats. Vision Res 40, 2201–2209.
42.Nathan, J., Reh, R., Ankoudinova, I., Ankoudinova, G., Chang, B., Heckenlively, J. R., Hurley, J. B. (2006). Scotopic and photopic visual thresholds and spatial and temporal discrimination by behavior of mice in a water maze. Photochem Photobiol 82, 1489–1494.
43.Prusky, G. T., Alam, N. M., Beekman, S., Douglas, R. M. (2004). Rapid quantification of adult and developing mouse spatial vision using a virtual optomotor system. Invest Ophthalmol Vis Sci 45, 4611–4616.
44.Abdeljalil, J., Hamid, M., Abel-Mouttalib, O., Stephane, R., Raymond, R., Johan, A., Jose, S., Chambon, P., Serge, P. (2005). The optomotor response: a robust first-line screening method for mice. Vision Res 45, 1439–1446.
45.Schmucker, C., Schaeffel, F. (2006). Contrast sensitivity of wildtype mice wearing diffusers or spectacle lenses, and the effect of atropine. Vision Res 46, 678–687.
46.Lyubarsky, A. L., Daniele, L. L., Pugh, E. N. J. (2004). From candelas to photoisomerizations in the mouse eye by rhodopsin bleaching in situ and the light-rearing dependence of the major components of the mouse ERG. Vision Res 44, 3235–3251.
47.Soucy, E., Wang, Y., Nirenberg, S., Nathans, J., Meister, M. (1998). A novel signalling pathway from rod photorceptors to ganglion cells in mammalian retina. Neuron 21, 481–493.
48.Pennesi, M. E., Lyubarsky, A. L., Pugh, E. N., Jr. (1998). Extreme responsiveness of the pupil of the dark-adapted mouse to steady retinal illumination. Invest Ophthalmol Vis Sci 39, 2148–2156.
49.Lennie, P., Pokorny, J., Smith, V. C. (1993). Luminance. J Opt Soc Am A 10, 1283–1293.
50.Prusky, G. T., Douglas, R. M. (2004). Characterization of mouse cortical spatial vision. Vision Res 44, 3411–3418.
51.Birch, D. G., Jacobs, G. H. (1979). Spatial contrast sensitivity in albino and pigmented rats. Vision Res 19, 933–937.
52.Wong, A. A., Brown, R. E. (2006). Visual detection, pattern discrimination and visual acuity in 14 strains of mice. Genes, Brain Behav 5, 389–403.
Mouse Cone Pigments and Vision |
373 |
53.Jacobs, G. H., Fenwick, J. A., Williams, G. A. (2001). Cone-based vision of rats for ultraviolet and visible lights. J Exp Biol 204, 2439–2446.
54.Toda, K., Bush, R. A., Humphries, P., Sieving, P. A. (1999). The electroretinogram of the rhodopsin knockout mouse. Vis Neurosci 16, 391–398.
55.Jaissle, G., May, C. A., Reinhard, J., Kohler, K., Fauser, S., Lutgen-Drecoll, E., Zrenner, E., Seeliger, M. W. (2001). Evaluation of the rhodopsin knockout mouse as a model of pure cone function. Invest Ophthalmol Vis Sci 42, 506–513.
56.Lyubarsky, A. L., Lem, J., Chen, J., Falsini, B., Iannaccone, A., Pugh Jr., E. N. (2002). Functionally rodless mice: transgenic models for investigation of cone function in retinal disease and therapy. Vision Res 42, 401–415.
57.Biel, M., Seeliger, M., Pfeifer, A., Kohler, K., Gerstiner, A., Ludwig, A., Jaissle, G., Fauser, S., Zrenner, E., Hofman, F. (1999). Selective loss of cone function in mice lacking the cyclic nucleotide-gated channel CNG3. Proc Natl Acad Sci U S A 96, 7553–7557.
58.Foster, R. G. (2002). Keeping track of time. Invest Ophthalmol Vis Science 43, 1286– 1298.
59.Semo, M., Peirson, S., Lupi, D., Lucas, R. J., Jeffrey, G., Foster, R. G. (2003). Melanopsin retinal ganglion cells and the maintenance of circadian and pupillary responses to light in aged rodless/coneless (rd/rd cl) mice. Eur J Neurosci 17, 1793–1801.
60.Jacobs, G. H., Rowe, M. P. (2004). Evolution of vertebrate colour vision. Clin Exp Optom 87, 206–216.
61.Shaaban, S. A., Crognale, M. A., Calderone, J. B., Huang, J., Jacobs, G. H., Deeb, S. S. (1998). Transgenic mice expressing a functional human photopigment. Invest Ophthalmol Vis Sci 39, 1036–1043.
62.Jacobs, G. H., Fenwick, J. C., Calderone, J. B., Deeb, S. S. (1999). Human cone pigment expressed in transgenic mice yields altered vision. J Neurosci 19, 3258–3265.
63.Smallwood, P. M., Olveczky, B. P., Williams, D. A., Jacobs, G. H., Reese, B. E., Meister, M., Nathans, J. (2003). Genetically engineered mice with an additional class of cone photoreceptors: Implications for the evolution of color vision. Proc Natl Acad Sci U S A 100, 11706–11711.
64.Onishi, A., Hasegawa, J., Imai, H., Chisaka, O., Ueda, Y., Honda, Y., Tachibana, M., Shichida, Y. (2005). Generation of knock-in mice carrying third cones with spectral sensitivity different from S and L cones. Zool Sci 22, 1145–1156.
65.Jacobs, G.H., Williams, G.A., Cahill, H., Nathans, J. (2007) Emergence of novel color vision in mice engineered to express a human cone photopigment. Science 315, 1723–1725.
66.Chang, B., Hawes, N. L., Hurd, R. E., Wang, J., Howell, D., Davisson, M. T., Roderick, T. H., Nusinowitz, S., Heckenlively, J. R. (2005). Mouse models of ocular disease. Vis Neurosci 22, 587–593.
67.Jacobs, G. H., Calderone, J. B., Fenwick, J. A., Krogh, K., Williams, G. A. (2003). Visual adaptations in a diurnal rodent, Octodon degus. J Comp Physiol A 189, 347–361.