Hostname: page-component-54dcc4c588-2bdfx Total loading time: 0 Render date: 2025-10-11T11:24:51.820Z Has data issue: false hasContentIssue false
  • English
  • Français

The Tennessee Mouse Genome Consortium: Identification of ocular mutants

Published online by Cambridge University Press:  06 December 2005

MONICA M. JABLONSKI ,
XIAOFEI WANG ,
LU LU ,
DARLA R. MILLER ,
EUGENE M. RINCHIK ,
ROBERT W. WILLIAMS  and
DANIEL GOLDOWITZ
MONICA M. JABLONSKI
Affiliation:
Department of Ophthalmology, University of Tennessee Health Science Center, Memphis Center of Genomics and Bioinformatics, University of Tennessee Health Science Center, Memphis Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis Tennessee Mouse Genome Consortium
XIAOFEI WANG
Affiliation:
Department of Ophthalmology, University of Tennessee Health Science Center, Memphis Center of Genomics and Bioinformatics, University of Tennessee Health Science Center, Memphis Tennessee Mouse Genome Consortium
LU LU
Affiliation:
Center of Genomics and Bioinformatics, University of Tennessee Health Science Center, Memphis Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis Tennessee Mouse Genome Consortium
DARLA R. MILLER
Affiliation:
Life Sciences Division, Oak Ridge National Laboratory, Oak Ridge Tennessee Mouse Genome Consortium
EUGENE M. RINCHIK
Affiliation:
Life Sciences Division, Oak Ridge National Laboratory, Oak Ridge Tennessee Mouse Genome Consortium
ROBERT W. WILLIAMS
Affiliation:
Center of Genomics and Bioinformatics, University of Tennessee Health Science Center, Memphis Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis Tennessee Mouse Genome Consortium
DANIEL GOLDOWITZ
Affiliation:
Center of Genomics and Bioinformatics, University of Tennessee Health Science Center, Memphis Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis Tennessee Mouse Genome Consortium
Get access Rights & Permissions [Opens in a new window]

Abstract

The Tennessee Mouse Genome Consortium (TMGC) is in its fifth year of a ethylnitrosourea (ENU)-based mutagenesis screen to detect recessive mutations that affect the eye and brain. Each pedigree is tested by various phenotyping domains including the eye, neurohistology, behavior, aging, ethanol, drug, social behavior, auditory, and epilepsy domains. The utilization of a highly efficient breeding protocol and coordination of various universities across Tennessee makes it possible for mice with ENU-induced mutations to be evaluated by nine distinct phenotyping domains within this large-scale project known as the TMGC. Our goal is to create mutant lines that model human diseases and disease syndromes and to make the mutant mice available to the scientific research community. Within the eye domain, mice are screened for anterior and posterior segment abnormalities using slit-lamp biomicroscopy, indirect ophthalmoscopy, fundus photography, eye weight, histology, and immunohistochemistry. As of January 2005, we have screened 958 pedigrees and 4800 mice, excluding those used in mapping studies. We have thus far identified seven pedigrees with primary ocular abnormalities. Six of the mutant pedigrees have retinal or subretinal aberrations, while the remaining pedigree presents with an abnormal eye size. Continued characterization of these mutant mice should in most cases lead to the identification of the mutated gene, as well as provide insight into the function of each gene. Mice from each of these pedigrees of mutant mice are available for distribution to researchers for independent study.

Keywords

MutagenesisEthylnitrosoureaOcular phenotypingRetinaMouse

Information

Type
Research Article
Information
Visual Neuroscience , Volume 22 , Issue 5 , September 2005 , pp. 595 - 604
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

Ahituv, N., Erven, A., Fuchs, H., Guy, K., Ashery-Padan, R., Williams, T., de Angelis, M.H., Avraham, K.B., & Steel, K.P. (2004). An ENU-induced mutation in AP-2alpha leads to middle ear and ocular defects in Doarad mice. Mammalian Genome 15, 424–432.CrossRefGoogle Scholar
Ambati, J., Ambati, B.K., Yoo, S.H., Ianchulev, S., & Adamis, A.P. (2003). Age-related macular degeneration: Etiology, pathogenesis, and therapeutic strategies. Survey Ophthalmologyl 48, 257–293.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. Biomedical Central Genetics 2, 1.Google Scholar
Baker, E.J., Galloway, L., Jackson, B., Schmoyer, D., & Snoddy, J. (2004). MuTrack: A genome analysis system for large-scale mutagenesis in the mouse. BMC Bioinformatics 3, 11.CrossRefGoogle Scholar
Du, X., Tabeta, K., Hoebe, K., Liu, H., Mann, N., Mudd, S., Crozat, K., Sovath, S., Gong, X., & Beutler, B. (2004). Velvet, a dominant Egfr mutation that causes wavy hair and defective eyelid development in mice. Genetics 166, 331–340.CrossRefGoogle Scholar
Goldowitz, D., Frankel, W.N., Takahashi, J.S., Holtz-Vitaterna, M., Bult, C., Kibbe, W.A., Snoddy, J., Li, Y., Pretel, S., Yates, J., & Swanson, D.J. (2004). Large-scale mutagenesis of the mouse to understand the genetic bases of nervous system structure and function. Molecular Brain Research 132, 105.CrossRefGoogle Scholar
Graw, J., Neuhauser-Klaus, A., Loster, J., Klopp, N., & Favor, J. (2002). Ethylnitrosourea-induced base pair substitution affects splicing of the mouse gammaE-crystallin encoding gene leading to the expression of a hybrid protein and to a cataract. Genetics 161, 1633–1640.Google Scholar
Green, W. (1999). Histopathology of age-related macular degeneration. Molecular Vision 5, 27.Google 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
Johnson, D.K., Rinchik, E.M., Moustaid-Moussa, N., Miller, D.R., Williams, R.W., Michaud, E.J., Jablonski, M.M., Elberger, A., Hamre, K., Smeyne, R., & Goldowitz, D. (2005). Phenotype screening for genetically-determined age-onset disorders and increased longevity in ENU-mutagenized mice. Age 27, 75–90.CrossRefGoogle Scholar
Martin, A.C., Thornton, J.D., Liu, J., Wang, X., Zuo, J., Jablonski, M.M., Chaum, E., Zindy, F., & Skapek, S.X. (2004). Pathogenesis of persistent hyperplastic primary vitreous in mice lacking the arf tumor suppressor gene. Investigative Ophthalmology and Visual Science 45, 3387–3396.CrossRefGoogle Scholar
Ruberti, J.W., Curcio, C.A., Millican, C.L., Menco, B.P., Huang, J.D., & Johnson, M. (2003). Quick-freeze/deep-etch visualization of age-related lipid accumulation in Bruch's membrane. Investigative Ophthalmology and Visual Science 44, 1753–1759.CrossRefGoogle Scholar
Semenova, E., Wang, X.F., Jablonski, M.M., Levorse, J., & Tilghman, S.M. (2003). An engineered 800 kilobase deletion of Uchl3 and Lmo7 on mouse chromosome 14 causes defects in viability, postnatal growth and degeneration of muscle and retina. Human Molecular Genetics 12, 1301–1312.CrossRefGoogle Scholar
Thaung, C., West, K., Clark, B.J., McKie, L., Morgan, J.E., Arnold, K., Nolan, P.M., Peters, J., Hunter, A.J., Brown, S.D., Jackson, I.J., & Cross, S.H. (2002). Novel ENU-induced eye mutations in the mouse: Models for human eye disease. Human Molecular Genetics 11, 755–767.CrossRefGoogle Scholar
Vitaterna, M.H., King, D.P., Chang, A.M., Kornhauser, J.M., Lowrey, P.L., McDonald, J.D., Dove, W.F., Pinto, L.H., Turek, F.W., & Takahashi, J.S. (1994). Mutagenesis and mapping of a mouse gene, clock, essential for circadian behavior. Science 264, 719–725.CrossRefGoogle Scholar