title: Analysis of lens cell fate and eye morphogenesis in transgenic mice ablated for cells of the lens lineage.
abstract: Transgenic mice carrying the diphtheria toxin A gene driven by mouse gamma 2-crystallin promoter sequences manifest microphthalmia due to ablation of fiber cells in the ocular lens. Here we map ablation events in the lens by crossing animals hemizygous for the ablation construct with transgenic mice homozygous for the in situ lacZ reporter gene driven by identical gamma 2-crystallin promoter sequences. By comparing the spatial distribution of lacZ-expressing cells and the profile of gamma-crystallin gene expression in the lenses of normal and microphthalmic offspring, the contributions of specific cell types to lens development were examined. The results suggest that phenotypically and developmentally distinct populations of lens fiber cells are able to contribute to the lens nucleus during organogenesis. We also show that dosage of the transgene and its site of integration influence the extent of ablation. In those mice homozygous for the transgene and completely lacking cells of the lens lineage, we show that the sclera, cornea, and ciliary epithelium are reduced in size but, otherwise, reasonably well formed. In contrast, the anterior chamber, iris, and vitreous body are not discernible while the sensory retina is highly convoluted and extensively fills the vitreous chamber.
authors.affiliation: Division of Cancer Research, Mount Sinai Hospital Research Institute, Toronto, Ontario, Canada.
authors.forename: M L
authors.initials: ML
authors.lastname: Breitman
authors.forename: D M
authors.initials: DM
authors.lastname: Bryce
authors.forename: E
authors.initials: E
authors.lastname: Giddens
authors.forename: S
authors.initials: S
authors.lastname: Clapoff
authors.forename: D
authors.initials: D
authors.lastname: Goring
authors.forename: L C
authors.initials: LC
authors.lastname: Tsui
authors.forename: G K
authors.initials: GK
authors.lastname: Klintworth
authors.forename: A
authors.initials: A
authors.lastname: Bernstein
mesh_terms: D000818:Animals; D003001:Cloning, Molecular; D003433:Crosses, Genetic; D003459:Crystallins / Q000235:genetics*; D004247:DNA / Q000235:genetics; D004167:Diphtheria Toxin / Q000235:genetics; D005260:Female; D015870:Gene Expression; D005796:Genes; D005838:Genotype; D006720:Homozygote; D007908:Lens, Crystalline / Q000002:abnormalities* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008850:Microphthalmos / Q000235:genetics*; D009024:Morphogenesis; D010446:Peptide Fragments / Q000235:genetics; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000302:isolation & purification; D014158:Transcription, Genetic
chemical_list: D003459:Crystallins; D004167:Diphtheria Toxin; D010446:Peptide Fragments; D012333:RNA, Messenger; C029795:diphtheria toxin fragment A; D004247:DNA