Effects of elevated Pax6 expression and genetic background on mouse eye development.
OBJECTIVE
To analyze the effects of Pax6 overexpression and its interaction with genetic background on eye development.


METHODS
Histologic features of eyes from hemizygous PAX77(+/-) transgenic (high Pax6 gene dose) and wild-type mice were compared on different genetic backgrounds. Experimental PAX77(+/-)<-->wild-type and control wild-type<-->wild-type chimeras were analyzed to investigate the causes of abnormal eye development in PAX77(+/-) mice.


RESULTS
PAX77(+/-) mice showed an overlapping but distinct spectrum of eye abnormalities to Pax6(+/-) heterozygotes (low Pax6 dose). Some previously reported PAX77(+/-) eye abnormalities did not occur on all three genetic backgrounds examined. Several types of eye abnormalities occurred in the experimental PAX77(+/-)<-->wild-type chimeras, and they occurred more frequently in chimeras with higher contributions of PAX77(+/-) cells. Groups of RPE cells intruded into the optic nerve sheath, indicating that the boundary between the retina and optic nerve may be displaced. Both PAX77(+/-) and wild-type cells were involved in this ingression and in retinal folds, suggesting that neither effect was cell-autonomous. Cell-autonomous effects included failure of PAX77(+/-) and wild-type cells to mix normally and overrepresentation of PAX77(+/-) in the lens epithelium and RPE.


CONCLUSIONS
The extent of PAX77(+/-) eye abnormalities depended on PAX77(+/-) genotype, genetic background, and stochastic variation. Chimera analysis identified two types of cell-autonomous effects of the PAX77(+/-) genotype. Abnormal cell mixing between PAX77(+/-) and wild-type cells suggests altered expression of cell surface adhesion molecules. Some phenotypic differences between PAX77(+/-)<-->wild-type and Pax6(+/-)<-->wild-type chimeras may reflect differences in the levels of PAX77(+/-) and Pax6(+/-) contributions to chimeric lenses.
Chanas
Simon A
SA
Division of Reproductive and Developmental Sciences, Genes and Development Group, University of Edinburgh, Edinburgh, Scotland, United Kingdom.
Collinson
J Martin
JM
Ramaesh
Thaya
T
Dorà
Natalie
N
Kleinjan
Dirk A
DA
Hill
Robert E
RE
West
John D
JD
D000818:Animals; D002678:Chimera / Q000235:genetics*; D003433:Crosses, Genetic; D005123:Eye / Q000196:embryology*; D005124:Eye Abnormalities / Q000235:genetics*; D005136:Eye Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism
D005136:Eye Proteins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D012097:Repressor Proteins