Hostname: page-component-74656f9884-8r8nv Total loading time: 0 Render date: 2026-11-10T21:57:27.411Z Has data issue: false hasContentIssue false
  • English
  • Français

Mouse models of ocular diseases

Published online by Cambridge University Press:  06 December 2005

B. CHANG ,
N.L. HAWES ,
R.E. HURD ,
J. WANG ,
D. HOWELL ,
M.T. DAVISSON ,
T.H. RODERICK ,
S. NUSINOWITZ  and
J.R. HECKENLIVELY
B. CHANG
Affiliation:
The Jackson Laboratory, Bar Harbor
N.L. HAWES
Affiliation:
The Jackson Laboratory, Bar Harbor
R.E. HURD
Affiliation:
The Jackson Laboratory, Bar Harbor
J. WANG
Affiliation:
The Jackson Laboratory, Bar Harbor
D. HOWELL
Affiliation:
The Jackson Laboratory, Bar Harbor
M.T. DAVISSON
Affiliation:
The Jackson Laboratory, Bar Harbor
T.H. RODERICK
Affiliation:
The Jackson Laboratory, Bar Harbor
S. NUSINOWITZ
Affiliation:
Jules Stein Eye Institute, and Harbor-UCLA Medical Center, Torrance
J.R. HECKENLIVELY
Affiliation:
W.K. Kellogg Eye Center, The University of Michigan, 1000 Wall Street, Ann Arbor
Get access Rights & Permissions [Opens in a new window]

Abstract

The Jackson Laboratory, having the world's largest collection of mouse mutant stocks and genetically diverse inbred strains, is an ideal place to discover genetically determined eye variations and disorders. In this paper, we list and describe mouse models for ocular research available from Mouse Eye Mutant Resource at The Jackson Laboratory. While screening mouse strains and stocks at The Jackson Laboratory (TJL) for genetic mouse models of human ocular disorders, we have identified numerous spontaneous or naturally occurring mutants. We characterized these mutants using serial indirect ophthalmoscopy, fundus photography, electroretinography (ERG) and histology, and performed genetic analysis including linkage studies and gene identification. Utilizing ophthalmoscopy, electroretinography, and histology, to date we have discovered 109 new disorders affecting all aspects of the eye including the lid, cornea, iris, lens, and retina, resulting in corneal disorders, glaucoma, cataracts, and retinal degenerations. The number of known serious or disabling eye diseases in humans is large and affects millions of people each year. Yet research on these diseases frequently is limited by the obvious restrictions on studying pathophysiologic processes in the human eye. Likewise, many human ocular diseases are genetic in origin, but appropriate families often are not readily available for genetic studies. Mouse models of inherited ocular disease provide powerful tools for rapid genetic analysis, characterization, and gene identification. Because of the great similarity among mammalian genomes, these findings in mice have direct relevance to the homologous human conditions.

Keywords

Mouse modelsRetinal degenerationCataractGlaucomaGene mapping

Information

Type
Research Article
Information
Visual Neuroscience , Volume 22 , Issue 5 , September 2005 , pp. 587 - 593
Copyright
© 2005 Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Article purchase

Temporarily unavailable

References

REFERENCES

Akhmedov, N.B., Pirie, N.I., Chang, B., Rappoport, A.L., Hawes, N.L., Nishina, P.M., Nusinowitz, S., Heckenlively, J.R., Roderick, T.H., Kozak, C.A., Danciger, M., Davisson, M.T., & Farber, D.B. (2000). A deletion in a photoreceptor-specific nuclear receptor mRNA causes retinal degeneration in the rd7 mouse. Proceedings of the National Academy of Sciences of the U.S.A. 97, 5551–5556.CrossRefGoogle Scholar
Anderson, M.G., Smith, R.S., Savinova, O.V., Hawes, N.L., Chang, B., Zabaleta, A., Wilpan, R., Heckenlively, J.R., Davisson, M., & John, S.W. (2001). Genetic modification of glaucoma associated phenotypes between AKXD-28/Ty and DBA/2J mice. BMC Genetics 2(1), 1.CrossRefGoogle Scholar
Anderson, M.G., Smith, R.S., Hawes, N.L., Zabaleta, A., Chang, B., Wiggs, J.L., & John, S.W. (2002). Mutations in genes encoding melanosomal proteins cause pigmentary glaucoma in DBA/2J mice. Nature Genetics 30, 81–85.CrossRefGoogle Scholar
Boatright, J.H., Rengarajan, K., Pardue, M.T., German Moring, A.J., Nickerson, J.M., Hawes, N.L., & Chang, B. (2003). Developmental analysis of the rd10 mouse. Investigative Ophthalmology and Visual Science 44, ARVO E-Abstract 4536.Google Scholar
Bronson, R.T., Lake, B.D., Cook, S., Taylor, S., & Davisson, M.T. (1993). Motor neuron degeneration of mice is a model of neuronal ceroid lipofuscinosis (Batten's disease). Annual Neurology 33, 381–385.CrossRefGoogle Scholar
Bronson, R.T., Donahue, L.R., Johnson, K.R., Tanner, A., Lane, P.W., & Faust, J.R. (1998). Neuronal ceroid lipofuscinosis (nclf), a new disorder of the mouse linked to chromosome 9. American Journal of Medical Genetics 77, 289–297.3.0.CO;2-I>CrossRefGoogle Scholar
Buchner, D.A., Seburn, K.L., Frankel, W.N., & Meisler, M.H. (2004). Three ENU-induced neurological mutations in the pore loop of sodium channel Scn8a (Na(v)1.6) and a genetically linked retinal mutation, rd13. Mammalian Genome 15(5), 344–51.Google Scholar
Burmeister, M., Novak, J., Liang, M.Y., Basu, S., Ploder, L., Hawes, N.L., Vidgen, D., Hoover, F., Goldman, D., Kalnins, V.I., Roderick, T.H., Taylor, B.A., Hankin, M.H., & McInnes, R.R. (1996). Ocular retardation mouse caused by Chx10 homeobox null allele: Impaired retinal progenitor proliferation and bipolar cell differentiation. Nature Genetics 12(4), 376–384.CrossRefGoogle Scholar
Chang, B., Heckenlively, J.R., Hawes, N.L., & Roderick, T.H. (1993). New mouse primary retinal degeneration (rd-3). Genomics 16, 45–49.CrossRefGoogle Scholar
Chang, B., Bronson, R.T., Hawes, N.L., Roderick, T.H., Peng, C., Hageman, G.S., & Heckenlively, J.R. (1994). A retinal degeneration in motor neuron degeneration: A mouse model of ceroid lipofuscinosis. Investigative Ophthalmology and Visual Science 35, 1071–1076.Google Scholar
Chang, B., Hageman, G.S., Heckenlively, J.R., Hawes, N.L., Peng, C., Roderick, T.H., & Davisson, M.T. (1996a). A mouse model for retinitis punctatus albescens: a new pathologic finding for retinal white dots. Investigative Ophthalmology and Visual Science 37(Suppl.), S505 (Abstract).Google Scholar
Chang, B., Hawes, N.L., Smith, R.S., Heckenlively, J.R., Davisson, M.T., & Roderick, T.H. (1996b). Chromosomal localization of a new mouse lens opacity gene (lop18). Genomics 36, 171–173.Google Scholar
Chang, B., Heckenlively, J.R., Hawes, N.L., & Davisson, M.T. (1998). A new mouse model of retinal dysplasia and degeneration (rd7). Investigative Ophthalmology and Visual Science 39(Suppl.), S880 (Abstract).Google Scholar
Chang, B., Hawes, N.L., Nishina, P.M., Smith, R.S., Davisson, M.T., & Heckenlively, J.R. (1999a). Two new mouse models of retinal degeneration (rd8 and Rd9). Investigative Ophthalmology and Visual Science 40(Suppl.), S976 (Abstract).Google Scholar
Chang, B., Smith, R.S., Hawes, N.L., Anderson, M.G., Zabaleta, A., Savinova, O., Roderick, T.H., Heckenlively, J.R., Davisson, M.T., & John, S.W. (1999b). Interacting loci cause severe iris atrophy and glaucoma in DBA/2J mice. Nature Genetics 21, 405–409.Google Scholar
Chang, B., Hawes, N.L., Roderick, T.H., Smith, R.S., Heckenlively, J.R., Horwitz, J., & Davisson, M.T. (1999c). Identification of a missense mutation in the alphaA-crystallin gene of the lop18 mouse. Molecular Vision 5, 21.Google Scholar
Chang, B., Hawes, N.L., Hurd, R.E., Davisson, M.T., Nusinowitz, S., & Heckenlively, J.R. (2000). A new mouse retinal degeneration (rd10) caused by a missense mutation in exon 13 of the beta-subunit of rod phosphodiesterase gene. Investigative Ophthalmology and Visual Science 41(Suppl.), S533 (Abstract).Google Scholar
Chang, B., Hawes, N.L., Hurd, R.E., Davisson, M.T., Nusinowitz, S., & Heckenlively, J.R. (2001a). A new mouse model of cone photoreceptor function loss (cpfl1). Investigative Ophthalmology and Visual Science 42(Suppl.), S527 (Abstract).Google Scholar
Chang, B., Smith. R.S., Peters. M., Savinova, O.V., Hawes, N.L., Zabaleta, A., Nusinowitz, S., Martin, J.E., Davisson, M.L., Cepko, C.L., Hogan, B.L., & John, S.W. (2001b). Haploinsufficient Bmp4 ocular phenotypes include anterior segment dysgenesis with elevated intraocular pressure. BMC Genetics 2(1), 18.Google Scholar
Chang, B., Wang, X., Hawes, N.L., Ojakian, R., Davisson, M.T., Lo, W.K., & Gong, X. (2002a). A Gja8 (Cx50) point mutation causes an alteration of alpha 3 connexin (Cx46) in semi-dominant cataracts of Lop10 mice. Human Molecular Genetics 11, 507–513.Google Scholar
Chang, B., Hawes, N.L., Hurd, R.E., Davisson, M.T., Nusinowitz, S., & Heckenlively, J.R. (2002b). A point mutation in the Rpe65 gene causes retinal degeneration (rd12) in mice. Investigative Ophthalmology and Visual Science 43, ARVO E-Abstract 3670.Google Scholar
Chang, B., Hawes, N.L., Hurd, R.E., Davisson, M.T., Nusinowitz, S., & Heckenlively, J.R. (2002c). Retinal degeneration mutants in the mouse. Vision Research 42(4), 517–525.Google Scholar
Chang, B., Hawes, N.L., Hurd, R.E., Miller, R.L., Davisson, M.T., Nusinowitz, S., & Heckenlively, J.R. (2003). A gene responsible for light-induced visual impairment (lvi) in mice. Investigative Ophthalmology and Visual Science 44, ARVO E-Abstract 4532.Google Scholar
Chang, B., Hawes, N.L., Hurd, R.E., Wang, J., Davisson, M.T., Nusinowitz, S., & Heckenlively, J.R. (2004). Selective loss of ERG b-wave caused by an autosomal recessive mutation in mice. Investigative Ophthalmology and Visual Science 45, ARVO E-Abstract 1019.Google Scholar
Chang, B., Hawes, N.L., Hurd, R.E., Wang, J., Davisson, M.T., Nusinowitz, S., & Heckenlively, J.R. (2005). A new mouse model of retinal degeneration (rd13). Investigative Ophthalmology and Visual Science 46, ARVO E-Abstract 3173.Google Scholar
Danciger, J.S., Danciger, M., Nusinowitz, S., Rickabaugh, T., & Farber, D.B. (1999). Genetic and physical maps of the mouse rd3 locus, exclusion of the ortholog of USH2A. Mammalian Genome 10(7), 657–661.CrossRefGoogle Scholar
Danciger, M., Hendrickson, J., Rao, N., Chang, B., Udar, N.S., Small, K.W., Davisson, M.T., & Farber, D.B. (2000). Positional cloning studies of the Rd4 retinal degeneration. Investigative Ophthalmology and Visual Science 41(Suppl.), S203 (ARVO-Abstract).Google Scholar
Donahue, L.R., Chang, B., Subburaman, M., Miyakoshi, N., Wergedal, J.E., Baylink, D.J., Hawes, N.L., Rosen, C.J., Ward-Bailey, P., Zheng, Q.Y., Bronson, R.T., Johnson, K.R., & Davisson, M.T. (2003). A missense mutation in the mouse Col2al gene causes spondyloepiphyseal dysplasia, hearing loss, and retinoschisis. Journal of Bone and Mineral Research 18, 1612–1621.CrossRefGoogle Scholar
Haider, N.B., Naggert, J.K., & Nishina, P.M. (2001). Excess cone cell proliferation due to lack of a functional NR2E3 causes retinal dysplasia and degeneration in rd7/rd7 mice. Human Molecular Genetics 10(16), 1619–26.CrossRefGoogle Scholar
Hawes, N.L. & Roderick, T.H. (1990). Linkage of ocular retardation (or). Mouse Genome 87, 93.Google Scholar
Hawes, N.L., Smith, R.S., Chang, B., Davisson, M., Heckenlively, J.R., & John, S.W. (1999). Mouse fundus photography and angiography: A catalogue of normal and mutant phenotypes. Molecular Vision 5, 22.Google Scholar
Hawes, N.L., Chang, B., Hageman, G.S., Nusinowitz, S., Nishina, P.M., Schneider, B.S., Smith, R.S., Roderick, T.H., Davisson, M.T., & Heckenlively, J.R. (2000). Retinal degeneration 6 (rd 6): A new mouse model for human retinitis punctata albescens. Investigative Ophthalmology and Visual Science 41, 3149–3157.Google Scholar
Hawes, N.L., Chang, B., Hurd, R.E., Nusinowitz, S., Heckenlively, J.R., & Davisson, M.T. (2002). A new mouse model of retinal degeneration (rd11). Investigative Ophthalmology and Visual Science 43, ARVO E-Abstract 3669.Google Scholar
Hawes, N.L., Hurd, R.E., Haider, N., Davisson, M.T., Nusinowitz, S., Heckenlively, J.R., & Chang, B. (2003). A new mouse model of cone photoreceptor function loss (Cpfl2). Investigative Ophthalmology and Visual Science 44, ARVO E-Abstract 4532.Google Scholar
Hawes, N.L., Hurd, R.E., Wang, J., Davisson, M.T., Nusinowitz, S., Heckenlively, J.R., & Chang, B. (2004). A new mouse model of cone photoreceptor function loss (Cpfl4). Investigative Ophthalmology and Visual Science 45h, ARVO E-Abstract 3590.Google Scholar
Hawes, N.L., Hurd, R.E., Wang, J., Davisson, M.T., Nusinowitz, S., Heckenlively, J.R., & Chang, B. (2005). A new mouse model of retinal degeneration (rd15) with retinal outer plexiform dystrophy. Investigative Ophthalmology and Visual Science 46, ARVO E-Abstract 3175.Google Scholar
Heckenlively, J.R., Chang, B., Erway, L.C., Peng, C., Hawes, N.L., Hageman, G.S., & Roderick, T.H. (1995). Mouse model for Usher syndrome: Linkage mapping suggests homology to Usher type I reported at human chromosome 11p15. Proceedings of the National Academy of Sciences of the U.S.A. 92, 11100–11104.CrossRefGoogle Scholar
Heckenlively, J.R., Hawes, N.L., Friedlander, M., Nusinowitz, S., Hurd, R., Davisson, M., & Chang, B. (2003). Mouse model of subretinal neovascularization with choroidal anastomosis. Retina 23, 518–522.CrossRefGoogle Scholar
Heckenlively, J.R., Dacey, M.S., Hawes, N.L., Hurd, R., Alexander, J.J., Hauswirth, W.W., Nusinowitz, S., Hitchcock, P.F., & Chang, B. (2005). Cone photoreceptor function loss-3 (Cpfl3), a new mouse model of achromatopsia due to missense mutation in GNAT2. Investigative Ophthalmology and Visual Science 46, ARVO E-Abstract 3190.Google Scholar
Ikeda, S., Hawes, N.L., Chang, B., Avery, C.S., Smith, R.S., & Nishina, P.M. (1999). Severe ocular abnormalities in C57BL/6 but not in 129/Sv p53-deficient mice. Investigative Ophthalmology and Visual Science 40, 1874–1878.Google Scholar
Ikeda, S., Cunningham, L.A., Boggess, D., Hobson, C.D., Sundberg, J.P., Naggert, J.K., Smith, R.S., & Nishina, P.M. (2003). Aberrant actin cytoskeleton leads to accelerated proliferation of corneal epithelial cells in mice deficient for destrin (actin depolymerizing factor). Human Molecular Genetics 12, 1029–1037.CrossRefGoogle Scholar
John, S.W., Smith, R.S., Savinova, O.V., Hawes, N.L., Chang, B., Turnbull, D., Davisson, M., Roderick, T.H., & Heckenlively, J.R. (1998). Essential iris atrophy, pigment dispersion, and glaucoma in DBA/2J mice. Investigative Ophthalmology and Visual Science 39, 951–962.Google Scholar
Kameya, S., Hawes, N.L., Chang, B., Heckenlively, J.R., Naggert, J.K., & Nishina, P.M. (2002). Mfrp, a gene encoding a frizzled related protein, is mutated in the mouse retinal degeneration 6. Human Molecular Genetics 11(16), 1879–1886.CrossRefGoogle Scholar
McKusick, V.A. (1998). Mendelian Inheritance in Man. Baltimore, Maryland: The Johns Hopkins University Press.
Mehalow, A.K., Kameya, S., Smith, R.S., Hawes, N.L., Denegre, J.M., Young, J.A., Bechtold, L., Haider, N.B., Tepass, U., Heckenlively, J.R., Chang, B., Naggert, J.K., & Nishina, P.M. (2003). CRB1 is essential for external limiting membrane integrity and photoreceptor morphogenesis in the mammalian retina. Human Molecular Genetics 12(17), 2179–89.CrossRefGoogle Scholar
Noben-Trauth, K., Naggert, J.K., North, M.A., & Nishina, P.M. (1996). A candidate gene for the mouse mutation tubby. Nature 380(6574), 534–538.CrossRefGoogle Scholar
Nusinowitz, S., Chang, B., Reichenbach, A., Hawes, N.L., Hurd, R.E., Donahue, L., Bronson, R., Wolburg, H., Davisson, M.T., & Heckenlively, J.R. (2001). A mouse model of retinoschisis caused by an autosomal recessive mutation. Investigative Ophthalmology and Visual Science 42(4), S767.Google Scholar
Pang, J., Chang, B., Heckenlively, J., Hawes, N.L., Nusinowitz, S., Noorwez, S.M., McDowell, J.H., Timmers, A.M., & Hauswirth, W.W. (2004). Gene therapy restores vision in a natural model of RPE65 Leber congenital amaurosis: The rd12 mouse. Investigative Ophthalmology and Visual Science 45, ARVO E-Abstract 3486.Google Scholar
Pieke-Dahl, S., Ohlemiller, K.K., McGee, J., Walsh, E.J., & Kimberling, W.J. (1997). Hearing loss in the RBF/DnJ mouse, a proposed animal model of Usher syndrome type IIa. Hearing Research 112(1–2), 1–12.Google Scholar
Robinson, G.C & Jan, J.F. (1993). Acquired ocular visual impairment in children. AJDC 147, 325–328.Google Scholar
Robinson, G.C., Jan, J.E., & Kinnis, C. (1987). Congenital ocular blindness in children, 1945–1984. AJDC 141, 1321–1324.CrossRefGoogle Scholar
Roderick, T.H., Chang, B., Hawes, N.L., & Heckenlively, J.R. (1997). A new dominant retinal degeneration (Rd4) associated with a chromosomal inversion in the mouse. Genomics 42, 393–396.CrossRefGoogle Scholar
Runge, P.E., Hawes, N.L., Heckenlively, J.R., Langley, S.H., & Roderick, T.H. (1992). Autosomal dominant mouse cataract (Lop-10), consistent differences of expression in heterozygotes. Investigative Ophthalmology and Visual Science 33, 3202–3208.Google Scholar
Smith, R.S., Hawes, N.L., Kuhlmann, S.D., Heckenlively, J.R., Chang, B., Roderick, T.H., & Sundberg, J.P. (1996). Corn1: A mouse model for corneal surface disease and neovascularization. Investigative Ophthalmology and Visual Science 37, 397–404.Google Scholar
Smith, R.S., John, S.W., Zabeleta, A., Davisson, M.T., Hawes, N.L., & Chang, B. (2000a). The bst locus on mouse chromosome 16 is associated with age-related subretinal neovascularization. Proceedings of the National Academy of Sciences of the U.S.A. 97(5), 2191–2195.Google Scholar
Smith, R.S., Hawes, N.L., Chang, B., Roderick, T.H., Akeson, E.C., Heckenlively, J.R., Gong, X., Wang, X., & Davisson, M.T. (2000b). Lop12, a mutation in mouse Crygd causing lens opacity similar to human Coppock cataract. Genomics 63, 314–320.Google Scholar
Taylor, B.A., Navin, A., & Phillips S.J. (1996). PCR-amplification of simple sequence repeat variants from pooled DNA samples for rapidly mapping new mutations of the mouse. Genomics 21, 626–632.Google Scholar
Talamas, E.J., Jackson, L., Chang, B., & Sidjanin, D. (2005). Mapping of the mouse lens opacity locus 11 (lop11). Investigative Ophthalmology and Visual Science 46, ARVO E-Abstract 823.Google Scholar
Varnum, D. (1981). “Nuclear cataract (nuc)”. Mouse News Letters 64, 59.Google Scholar
Young, K.A, Berry, M.L., Mahaffey, C.L., Saionz, J.R., Hawes, N.L., Chang, B., Zheng, Q.Y., Smith, R.S., Bronson, R.T., Nelson, R.J., & Simpson, E.M. (2002). Fierce: A new mouse deletion of Nr2e1; violent behaviour and ocular abnormalities are background-dependent. Behavioral Brain Research 132, 145–158.CrossRefGoogle Scholar
Zhang, J., Hawes, N.L., Wang, J., Harris, B.S., Hurd, R.E., Davisson, M.T., Heckenlively, J.R., & Chang, B. (2005). A new mouse model of retinal degeneration (rd14). Investigative Ophthalmology and Visual Science 46, ARVO E-Abstract 3170.Google Scholar