2022-10-14
uOttawa Insight Club
Skyra
Throughout the history of laboratory research, mice have been extensively used as mammalian model systems for human biology due to numerous advantages which include their small size, low cost, fast breeding times, and short lifespan1.
However, how similar are mice and humans really? Advances in biotechnology have facilitated quick and inexpensive whole genome sequencing techniques and direct sequence comparisons. The mouse genome contains 2.5Gb divided into 40 chromosomes compared to the
2.9Gb-sized human genome2. On average, the protein-coding genes of the mouse genome are 85% homologous to the human genome3.
When it comes to the visual system, there are several key anatomical differences.
1. Despite their diminutive size, the mouse eye is ten times bigger than the human eye in proportion to body size4. The shape of the mouse lens is more spherical than in humans and fills the majority of the vitreal cavity5,6. The mouse numerical aperture (NA) of 0.49 is over twice the NA of 0.18 in humans, which is advantageous for low-light night activity5.
2. Notably, mice lack a fovea, the highly cone-dense area of the retina responsible for high-acuity central vision in humans. Instead, cone density across the entire mouse retina is comparable to that of the peripheral retina of primates7,8. This results in an extended visual field of uniform optical focus6 and is evolutionarily adapted to the nocturnal prey nature of mice. Nevertheless, a recent study using population receptive field (pRF) mapping suggested that the mouse visual cortex may contain regions of increased spatial resolution to accommodate for detailed visual processing9.
3. Mice express only two photopigments in their cone photoreceptors: “blue-detecting” S-cones with a peak wavelength of 360nm, and “green-detecting” M-cones with a peak absorption wavelength of 511nm. In contrast to humans, mice lack the “red-detecting” L-cones and therefore, cannot distinguish between red and green5,10. The ability for chromatic discrimination in mice was enhanced upon knock-in expression of human L photopigment11,12.
Understanding and taking into account the differences between the mouse and human visual system is essential for translational studies as the mouse continues to be researched as an animal model.
References
1. Uhl, E. W. & Warner, N. J. Mouse Models as Predictors of Human Responses: Evolutionary Medicine. Curr. Pathobiol. Rep. 3, 219–223 (2015).
2. Chinwalla, A. T. et al. Initial sequencing and comparative analysis of the mouse genome. Nature 420, 520–562 (2002).
3. Makałowski, W., Zhang, J. & Boguski, M. S. Comparative analysis of 1196 orthologous mouse and human full-length mRNA and protein sequences. Genome Res. 6, 846–857 (1996).
4. Scammon, R. E. & Armstrong, E. L. On the growth of the human eyeball and optic nerve. J. Comp. Neurol. 38, 165–219 (1925).
5. Geng, Y. et al. Optical properties of the mouse eye. Biomed. Opt. Express 2, 717–738 (2011).
6. Sundin, O. H. The Mouse’s Eye and Mfrp : Not Quite Human. Ophthalmic Genet. 26, 153–155 (2005).
7. Huberman, A. D. & Niell, C. M. What can mice tell us about how vision works? Trends Neurosci. 34, 464–473 (2011).
8. Jeon, C.-J., Strettoi, E. & Masland, R. H. The major cell populations of the mouse retina. J. Neurosci. 18, 8936–8946 (1998).
9. van Beest, E. H. et al. Mouse visual cortex contains a region of enhanced spatial resolution. Nat. Commun. 12, 4029 (2021).
10. Nikonov, S. S., Kholodenko, R., Lem, J. & Pugh Jr, E. N. Physiological features of the S-and M-cone photoreceptors of wild-type mice from single-cell recordings. J. Gen. Physiol. 127, 359–374 (2006).
11. Jacobs, G. H., Williams, G. A., Cahill, H. & Nathans, J. Emergence of Novel Color Vision in Mice Engineered to Express a Human Cone Photopigment. Science 315, 1723–1725 (2007).
12. Onishi, A. et al. Generation of Knock-in Mice Carrying Third Cones with Spectral Sensitivity Different from S and L Cones. Zoolog. Sci. 22, 1145–1156 (2005).
Comentarios