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Comparative structural and functional analysis of photoreceptor neurons of Rho-/- mice reveal increased survival on C57BL/6J in comparison to 129Sv genetic background

Published online by Cambridge University Press:  10 September 2001

MARIAN M. HUMPHRIES ,
SOPHIE KIANG ,
NIAMH McNALLY ,
MARY ANNE DONOVAN ,
PAUL A. SIEVING ,
RONALD A. BUSH ,
SHIGEKI MACHIDA ,
THOMAS COTTER ,
AUDREY HOBSON  and
JANE FARRAR
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MARIAN M. HUMPHRIES
Affiliation:
The Ocular Genetics Unit, Institute of Genetics, Trinity College, Dublin 2, Ireland
SOPHIE KIANG
Affiliation:
The Ocular Genetics Unit, Institute of Genetics, Trinity College, Dublin 2, Ireland
NIAMH McNALLY
Affiliation:
The Ocular Genetics Unit, Institute of Genetics, Trinity College, Dublin 2, Ireland
MARY ANNE DONOVAN
Affiliation:
Department of Biochemistry, University College, Cork, Ireland
PAUL A. SIEVING
Affiliation:
W.K. Kellogg Eye Center, University of Michigan, Ann Arbor
RONALD A. BUSH
Affiliation:
W.K. Kellogg Eye Center, University of Michigan, Ann Arbor
SHIGEKI MACHIDA
Affiliation:
W.K. Kellogg Eye Center, University of Michigan, Ann Arbor
THOMAS COTTER
Affiliation:
Department of Biochemistry, University College, Cork, Ireland
AUDREY HOBSON
Affiliation:
The Ocular Genetics Unit, Institute of Genetics, Trinity College, Dublin 2, Ireland
JANE FARRAR
Affiliation:
The Ocular Genetics Unit, Institute of Genetics, Trinity College, Dublin 2, Ireland
PETE HUMPHRIES
Affiliation:
The Ocular Genetics Unit, Institute of Genetics, Trinity College, Dublin 2, Ireland
PAUL KENNA
Affiliation:
The Ocular Genetics Unit, Institute of Genetics, Trinity College, Dublin 2, Ireland
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Abstract

To explore the possible influence of defined genetic backgrounds on photoreceptor viability and function in mice carrying a targeted disruption of the rhodopsin gene, the severities of retinopathies in Rho-/- mice on C57BL/6J and 129Sv congenic backgrounds were compared by light microscopy and electroretinography and qualitatively by in situ end labeling of DNA in apoptotic photoreceptor nuclei of retinal sections. Cone photoreceptor viability and function were shown to deteriorate more slowly on the C57BL/6J background in comparison to that of the 129Sv, with significantly greater numbers of outer nuclear layer nuclei in the retinas of C57BL/6J mice at 3 and 4 months of age. Both amplitude and waveform features of the ERG were shown to be remarkably different in the two strains, indicating an approximately 6-fold difference in C57BL/6J Rho-/- mice compared to 129Sv Rho-/- mice at 80 days. Thus, in comparison with the 129Sv strain, genetic modifiers appear to constitute a component of the C57BL/6J background, the expression of which significantly protects cone photoreceptors from apoptotic death in a mutation-induced murine retinopathy. The differences in phenotype revealed in this study are sufficient in principle to provide a basis for comparisons to be made between QTLs in light-induced and mutation-induced systems.

Keywords

Mouse rhodopsin knockoutGenetic backgroundsModifiersElectroretinogram
Type
Research Article
Information
Visual Neuroscience , Volume 18 , Issue 3 , May 2001 , pp. 437 - 443
Copyright
2001 Cambridge University Press

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