Transient expression of theArftumor suppressor during male germ cell and eye development inArf-Crereporter mice

Abstract

conditional Arf-null mouse ͉ PDGF signaling ͉ spermatogenesis ͉ vitreal hyaloid vasculature

Arf tumor suppressor and miR-205 regulate cell adhesion and formation of extraembryonic endoderm from pluripotent stem cells

“…Arf is expressed in mitotically dividing spermatogonia, but not in primary spermatocyctes derived from them or in other cells within the testis (6,7). In unrelated studies, we determined that the levels of a single microRNA, miR-205, were selectively decreased by >15-fold in the Arf-null testes of postnatal day-18 mice, a time when p19 Arf levels in spermatogonia are maximal and are synchronously expressed throughout the developing seminiferous tubules.…”

“…5 B and C). Because we did not succeed in generating such cultures from Arf-null ES cells, we established ExEn cells from blastocysts containing "floxed" Arf alleles (Arf FL/FL ) (6) and deleted Arf exon-1β with a retrovirus encoding Cre recombinase. These Arf-null ExEn cells continued to proliferate continuously, and expression of ExEn markers was maintained, so Arf is not required for ExEn cell line viability and maintenance.…”

“…Paradoxically, the p19 Arf protein is physiologically expressed in a few disparate tissues during mouse development, including perivascular cells within the hyaloid vasculature of the eye (4-6), mitotically dividing spermatogonia within seminiferous tubules (6,7), and the fetal yolk sac (8). Inactivation of Arf results in blindness and reduced sperm production, but effects of Arf deletion on yolk sac development have not been investigated.…”

Small mitochondrial Arf (smArf) protein corrects p53-independent developmental defects of Arf tumor suppressor-deficient mice

“…As noted by others, the resulting ocular phenotype closely mimics persistent hyperplastic primary vitreous, a congenital disease of unknown etiology in children that can similarly erode the posterior lens capsule and lead to retinal detachment and blindness (34,35). The appearance of the accumulating mass within the vitreous of the developing eye depends on disruption of p19 Arfdependent suppression of platelet-derived growth factor-beta (PDGFβ) signaling within the hyaloid vasculature (35,36), so that targeted disruption of PDGF receptor-β signaling in the eye rescues blindness (37). By use of an optokinetic system that depends on reflexive head movement in the direction of a rotating visual field (38), functional and quantitative measurements of visual acuity allow any underlying histopathological defects to be prospectively identified (37).…”

“…The appearance of the accumulating mass within the vitreous of the developing eye depends on disruption of p19 Arfdependent suppression of platelet-derived growth factor-beta (PDGFβ) signaling within the hyaloid vasculature (35,36), so that targeted disruption of PDGF receptor-β signaling in the eye rescues blindness (37). By use of an optokinetic system that depends on reflexive head movement in the direction of a rotating visual field (38), functional and quantitative measurements of visual acuity allow any underlying histopathological defects to be prospectively identified (37). Arf-null mice lacking both p19 Arf and p15 smArf and M45A mutant mice lacking only p15 smArf were blind, whereas mice expressing smArf alone exhibited no detectable visual defects (Fig.…”