Altered retinal cell differentiation in the AP-3 delta mutant (Mocha) mouse.
Adaptor-related protein complex 3 delta 1 (Ap3d1) encodes the delta 1 subunit of an adaptor protein regulating intracellular vesicle-mediated transport, and the Ap3d-deletion mutant (Mocha) mouse undergoes rapid photoreceptor degeneration leading to blindness soon after birth. Previous microarray analysis revealed Ap3d down-regulation in the retina of mouse embryos specifically lacking cholinergic amacrine cells as a result of the absence of skeletal musculature. To investigate the role of Ap3d in the determination of retinal cell fate, the present study examined retinal morphology in newborn Ap3d-/- mice. The Ap3d-/- retina showed a complete absence of cholinergic amacrine cells and a decrease in parvalbumin-expressing amacrine cells and syntaxin- and VC1.1-expressing amacrine precursor cells, but had a normal number of cell layers and number of cells in each layer with no detectable difference in cell proliferation or apoptosis. These findings indicate that, despite having no apparent effect on the basic spatial organization of the retina at this stage of development, Ap3d could be involved in the regulation of progenitor cell competence and the eventual ratio of resulting differentiated cells. Finding the mouse mutant which phenocopies the eye defect seen in fetuses with no striated muscle was accomplished by the Systematic Subtractive Microarray Analysis Approach (SSMAA), explained in the discussion section.
Baguma-Nibasheka
Mark
M
Department of Anatomy and Neurobiology, Dalhousie University Faculty of Medicine, Halifax, NS, Canada.
Kablar
Boris
B
D033963:Adaptor Protein Complex 3; D033966:Adaptor Protein Complex beta Subunits; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D010320:Parvalbumins / Q000378:metabolism; D012160:Retina / Q000166:cytology*; D013234:Stem Cells / Q000166:cytology / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D033963:Adaptor Protein Complex 3; D033966:Adaptor Protein Complex beta Subunits; C113910:Ap3d1 protein, mouse; D010320:Parvalbumins; D014157:Transcription Factors