The Phosphoinosotide 3-Kinase Catalytic Subunit p110α is Required for Normal Lens Growth.
Signal transduction pathways influence lens growth, but little is known about the role(s) of the class 1A phosphoinositide 3-kinases (PI3Ks). To further investigate how signaling regulates lens growth, we generated and characterized mice in which the p110α and p110β catalytic subunits of PI3K were conditionally deleted in the mouse lens.



Floxed alleles of the catalytic subunits of PI3K were conditionally deleted in the lens by using MLR10-cre transgenic mice. Lenses of age-matched animals were dissected and photographed. Postnatal lenses were fixed, paraffin embedded, sectioned, and stained with hematoxylin-eosin. Cell proliferation was quantified by labeling S-phase cells in intact lenses with 5-ethynyl-2'-deoxyuridine. Protein kinase B (AKT) activation was examined by Western blotting.



Lens-specific deletion of p110α resulted in a significant reduction of eye and lens size, without compromising lens clarity. Conditional knockout of p110β had no effect on lens size or clarity, and deletion of both the p110α and p110β subunits resulted in a phenotype that resembled the p110α single-knockout phenotype. Levels of activated AKT were decreased more in p110α- than in p110β-deficient lenses. A significant reduction in proliferating cells in the germinative zone was observed on postnatal day 0 in p110α knockout mice, which was temporally correlated with decreased lens volume.



These data suggest that the class 1A PI3K signaling pathway plays an important role in the regulation of lens size by influencing the extent and spatial location of cell proliferation in the perinatal period.
Department of Physiology and Biophysics Stony Brook University, Stony Brook, New York, United States.
Caterina
C
Sellitto
Department of Physiology and Biophysics Stony Brook University, Stony Brook, New York, United States.
Leping
L
Li
School of Optometry and Vision Science, School of Medical Sciences, University of Auckland, Auckland, New Zealand.
Ehsan
E
Vaghefi
Department of Physiology, School of Medical Sciences, University of Auckland, Auckland, New Zealand.
Paul J
PJ
Donaldson
Department of Physiology and Biophysics Stony Brook University, Stony Brook, New York, United States 4Medical Service, Department of Veterans Affairs Medical Center, Northport, New York, United States.
Richard Z
RZ
Lin
Department of Physiology and Biophysics Stony Brook University, Stony Brook, New York, United States.
Thomas W
TW
White
D000818:Animals; D015153:Blotting, Western; D020134:Catalytic Domain; D049109:Cell Proliferation; D058534:Class I Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D007908:Lens, Crystalline / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C488371:p110delta protein, rat; D051057:Proto-Oncogene Proteins c-akt