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Mouse model resources for vision research.

Won J, Shi LY, Hicks W, Wang J, Hurd R, Naggert JK, Chang B, Nishina PM - J Ophthalmol (2010)

Bottom Line: Over 100 mutant lines from the Eye Mutant Resource and 60 mutant lines from the Translational Vision Research Models have been developed.The mutations in disease genes have been mapped and in some cases identified by direct sequencing.Here, we report 3 novel alleles of Crx(tvrm65), Rp1(tvrm64), and Rpe65(tvrm148) as successful examples of the TVRM program, that closely resemble previously reported knockout models.

View Article: PubMed Central - PubMed

Affiliation: The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609, USA.

ABSTRACT
The need for mouse models, with their well-developed genetics and similarity to human physiology and anatomy, is clear and their central role in furthering our understanding of human disease is readily apparent in the literature. Mice carrying mutations that alter developmental pathways or cellular function provide model systems for analyzing defects in comparable human disorders and for testing therapeutic strategies. Mutant mice also provide reproducible, experimental systems for elucidating pathways of normal development and function. Two programs, the Eye Mutant Resource and the Translational Vision Research Models, focused on providing such models to the vision research community are described herein. Over 100 mutant lines from the Eye Mutant Resource and 60 mutant lines from the Translational Vision Research Models have been developed. The ocular diseases of the mutant lines include a wide range of phenotypes, including cataracts, retinal dysplasia and degeneration, and abnormal blood vessel formation. The mutations in disease genes have been mapped and in some cases identified by direct sequencing. Here, we report 3 novel alleles of Crx(tvrm65), Rp1(tvrm64), and Rpe65(tvrm148) as successful examples of the TVRM program, that closely resemble previously reported knockout models.

No MeSH data available.


Related in: MedlinePlus

The Rpe65tvrm148 mouse model. (a) Mutation analysis by direct sequencing revealed that the homozygous Rpe65tvrm148 mouse harbored a missense mutation at aa residue 229, causing an amino acid change from Phe to Ser. The highlighted nucleotide indicates the mutation in the Rpe65tvrm148 mouse (left). RPE65 protein is an evolutionarily conserved protein, and F229 is a nearly invariant residue from human to zebra fish (right). (b) Retinal morphology at 1 and 4 months and 1 year of age was analyzed by light microscopy. ONL thinning was progressive, and IS/OS was shorter than controls at all ages examined. OSs: outer segments, ISs: inner segments, ONL: outer nuclear layer, OPL: outer plexiform layer, INL: inner nuclear layer. Scale bar  =  20 μm. (c, d) Physiological retinal function was analyzed by ERG at 4 weeks (c) and 17 weeks of age (d). The plotted amplitude was obtained at 9 weeks from control and Rpe65tvrm148 mice (c) or at 17 weeks from control and from homozygous Rpe65tvrm148 mice. N = 3.
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fig4: The Rpe65tvrm148 mouse model. (a) Mutation analysis by direct sequencing revealed that the homozygous Rpe65tvrm148 mouse harbored a missense mutation at aa residue 229, causing an amino acid change from Phe to Ser. The highlighted nucleotide indicates the mutation in the Rpe65tvrm148 mouse (left). RPE65 protein is an evolutionarily conserved protein, and F229 is a nearly invariant residue from human to zebra fish (right). (b) Retinal morphology at 1 and 4 months and 1 year of age was analyzed by light microscopy. ONL thinning was progressive, and IS/OS was shorter than controls at all ages examined. OSs: outer segments, ISs: inner segments, ONL: outer nuclear layer, OPL: outer plexiform layer, INL: inner nuclear layer. Scale bar = 20 μm. (c, d) Physiological retinal function was analyzed by ERG at 4 weeks (c) and 17 weeks of age (d). The plotted amplitude was obtained at 9 weeks from control and Rpe65tvrm148 mice (c) or at 17 weeks from control and from homozygous Rpe65tvrm148 mice. N = 3.

Mentions: The recessive tvrm148 mutation is characterized by late onset retinal spotting and by patches of depigmentation that is readily discernable by indirect ophthalmoscopy at 5 months of age (data not shown). The mutation mapped to Chr. 3 between markers, D3Mit147 and D3Mit19. Rpe65 was screened by direct sequencing for a mutation as it fell within the minimal interval identified, and the disease phenotype was similar to that reported for the Rpe65tmlTmr targeted knockout animal (herein referred to as Rpe65−/−) [63] and Rpe65rd12 [64] alleles. A T>C point mutation was found by direct sequencing of retinal cDNA from Rpe65tvrm148 mice and is expected to generate a mutant protein with an F229S point mutation (Figure 4(a)). F229 is evolutionarily conserved from humans to zebra fish but interestingly not in chimpanzee (Figure 4(a)).


Mouse model resources for vision research.

Won J, Shi LY, Hicks W, Wang J, Hurd R, Naggert JK, Chang B, Nishina PM - J Ophthalmol (2010)

The Rpe65tvrm148 mouse model. (a) Mutation analysis by direct sequencing revealed that the homozygous Rpe65tvrm148 mouse harbored a missense mutation at aa residue 229, causing an amino acid change from Phe to Ser. The highlighted nucleotide indicates the mutation in the Rpe65tvrm148 mouse (left). RPE65 protein is an evolutionarily conserved protein, and F229 is a nearly invariant residue from human to zebra fish (right). (b) Retinal morphology at 1 and 4 months and 1 year of age was analyzed by light microscopy. ONL thinning was progressive, and IS/OS was shorter than controls at all ages examined. OSs: outer segments, ISs: inner segments, ONL: outer nuclear layer, OPL: outer plexiform layer, INL: inner nuclear layer. Scale bar  =  20 μm. (c, d) Physiological retinal function was analyzed by ERG at 4 weeks (c) and 17 weeks of age (d). The plotted amplitude was obtained at 9 weeks from control and Rpe65tvrm148 mice (c) or at 17 weeks from control and from homozygous Rpe65tvrm148 mice. N = 3.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2968714&req=5

fig4: The Rpe65tvrm148 mouse model. (a) Mutation analysis by direct sequencing revealed that the homozygous Rpe65tvrm148 mouse harbored a missense mutation at aa residue 229, causing an amino acid change from Phe to Ser. The highlighted nucleotide indicates the mutation in the Rpe65tvrm148 mouse (left). RPE65 protein is an evolutionarily conserved protein, and F229 is a nearly invariant residue from human to zebra fish (right). (b) Retinal morphology at 1 and 4 months and 1 year of age was analyzed by light microscopy. ONL thinning was progressive, and IS/OS was shorter than controls at all ages examined. OSs: outer segments, ISs: inner segments, ONL: outer nuclear layer, OPL: outer plexiform layer, INL: inner nuclear layer. Scale bar = 20 μm. (c, d) Physiological retinal function was analyzed by ERG at 4 weeks (c) and 17 weeks of age (d). The plotted amplitude was obtained at 9 weeks from control and Rpe65tvrm148 mice (c) or at 17 weeks from control and from homozygous Rpe65tvrm148 mice. N = 3.
Mentions: The recessive tvrm148 mutation is characterized by late onset retinal spotting and by patches of depigmentation that is readily discernable by indirect ophthalmoscopy at 5 months of age (data not shown). The mutation mapped to Chr. 3 between markers, D3Mit147 and D3Mit19. Rpe65 was screened by direct sequencing for a mutation as it fell within the minimal interval identified, and the disease phenotype was similar to that reported for the Rpe65tmlTmr targeted knockout animal (herein referred to as Rpe65−/−) [63] and Rpe65rd12 [64] alleles. A T>C point mutation was found by direct sequencing of retinal cDNA from Rpe65tvrm148 mice and is expected to generate a mutant protein with an F229S point mutation (Figure 4(a)). F229 is evolutionarily conserved from humans to zebra fish but interestingly not in chimpanzee (Figure 4(a)).

Bottom Line: Over 100 mutant lines from the Eye Mutant Resource and 60 mutant lines from the Translational Vision Research Models have been developed.The mutations in disease genes have been mapped and in some cases identified by direct sequencing.Here, we report 3 novel alleles of Crx(tvrm65), Rp1(tvrm64), and Rpe65(tvrm148) as successful examples of the TVRM program, that closely resemble previously reported knockout models.

View Article: PubMed Central - PubMed

Affiliation: The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609, USA.

ABSTRACT
The need for mouse models, with their well-developed genetics and similarity to human physiology and anatomy, is clear and their central role in furthering our understanding of human disease is readily apparent in the literature. Mice carrying mutations that alter developmental pathways or cellular function provide model systems for analyzing defects in comparable human disorders and for testing therapeutic strategies. Mutant mice also provide reproducible, experimental systems for elucidating pathways of normal development and function. Two programs, the Eye Mutant Resource and the Translational Vision Research Models, focused on providing such models to the vision research community are described herein. Over 100 mutant lines from the Eye Mutant Resource and 60 mutant lines from the Translational Vision Research Models have been developed. The ocular diseases of the mutant lines include a wide range of phenotypes, including cataracts, retinal dysplasia and degeneration, and abnormal blood vessel formation. The mutations in disease genes have been mapped and in some cases identified by direct sequencing. Here, we report 3 novel alleles of Crx(tvrm65), Rp1(tvrm64), and Rpe65(tvrm148) as successful examples of the TVRM program, that closely resemble previously reported knockout models.

No MeSH data available.


Related in: MedlinePlus