Protecting against aging at the molecular level
High fidelity DNA replication during each cycle of cell division is required to maintain genomic stability and prevent chromosomal mutations and rearrangements that can cause disease and aging. Mutations in ATRX, a gene that encodes a protein that participates in DNA replication, are associated with X-linked mental retardation, various cancers, and developmental disorders, but the cellular functions of ATRX are still unclear. In this issue of the Journal of Clinical Investigation, researchers led by Nathalie Bérubé at the University of Western Ontario report on the effects of Atrx deficiency in mice. Using neural precursor cells (NPCs) from Atrx-deficient mice, Bérubé and colleagues found that loss of ATRX is associated with increased DNA damage. Additionally, mice lacking neural Atrx exhibited systemic endocrine dysfunction, shortened lifespans, and degenerative phenotypes similar to human premature aging disorders. These studies demonstrate that ATRX plays a critical role in maintaining the integrity of cellular DNA.
TITLE:
Atrx deficiency induces telomere dysfunction, endocrine defects, and reduced lifespan
AUTHOR CONTACT:
Nathalie G Bérubé
Children's Health Research Institute, The University of Western Ontario, London, ON, CAN
Phone: 519-685-8500 x 55066; Fax: 519-685-8616; E-mail: nberube@uwo.ca
View this article at: http://www.jci.org/articles/view/65634?key=d3e4230ee774cca17a25
Researchers identify transcription factors that regulate retinal vascularization
The retina is a highly vascularized tissue, but too much or too little vascularization can lead to visual impairment and diseases such as familial exudative vitreoretinopathy or macular degeneration. In this issue of the Journal of Clinical Investigation, Alfred Nordheim and colleagues at Tuebingen University in Tuebingen, Germany, identified the DNA transcription factor SRF and its cofactors MRTF-A and MRTF-B as critical regulators of vascularization in the postnatal mouse eye. Loss of vascular Srf in adult mice led to the formation of microaneurysms and excess blood vessel formation similar to human retinal diseases such as retinal angiomatous proliferation and macular telangiectasia. These studies demonstrate that SRF plays an integral role in the development and homeostasis or the retinal vasculature and suggest that SRF could potentially serve as a therapeutic target in human retinal diseases.
TITLE:
Endothelial SRF/MRTF ablation causes vascular disease phenotypes in murine retinae
AUTHOR CONTACT:
Alfred Nordheim
Tuebingen University, Tuebingen, DEU
Phone: 4970712978898; E-mail: alfred.nordheim@uni-tuebingen.de
View this article at: http://www.jci.org/articles/view/64201?key=4dc1a65206b8018e0e4b
ALSO IN THIS ISSUE
TITLE:
Loss of acinar cell Ikka triggers spontaneous pancreatitis in mice
AUTHOR CONTACT:
Michael Karin
University of California, San Diego, La Jolla, CA, USA
Phone: 858-534-1361; Fax: 858-534-8158; E-mail: karinoffice@ucsd.edu
View this article at: http://www.jci.org/articles/view/64498?key=8da89eb7ab14951f7606
TITLE:
Natural variation in Fc glycosylation of HIV-specific antibodies impacts anti-viral activity
AUTHOR CONTACT:
Galit Alter
Massachusetts General Hospital, Charlestown, MA, USA
Phone: 617-724-0546; Fax: 617-726-5411; E-mail: galter@partners.org
View this article at: http://www.jci.org/articles/view/65708?key=259e1956bd16b3da2139
TITLE:
CCDC22 deficiency in humans blunts activation of pro-inflammatory NF-κB signaling
AUTHOR CONTACT:
Ezra Burstein
University of Texas Southwestern Medical Center, Dallas, TX, USA
Phone: 214-648-2008; Fax: 214-648-2022; E-mail: ezra.burstein@utsouthwestern.edu
View this article at: http://www.jci.org/articles/view/66466?key=e9513cca064259fdf788
TITLE:
HIF1α and HIF2α independently activate SRC to promote melanoma metastases
AUTHOR CONTACT:
William Kim
University of North Carolina, Chapel Hill, NC, USA
Phone: 919-966-4765; E-mail: wykim@med.unc.edu
View this article at: http://www.jci.org/articles/view/66715?key=f24859543559147acb78
TITLE:
Smoothened is a master regulator of adult liver repair
AUTHOR CONTACT:
Anna Mae Diehl
Duke University Medical Center, Durham, NC, USA
Phone: 919-684-4173; Fax: 919-684-4183; E-mail: diehl004@mc.duke.edu
View this article at: http://www.jci.org/articles/view/66904?key=05c91856cad4eb6a6fc7
TITLE:
Eosinophil pathogenicity mechanisms and therapeutics in neuromyelitis optica
AUTHOR CONTACT:
Alan Verkman
University of California, San Francisco, San Francisco, CA, USA
Phone: 415-476-8530; Fax: 415-665-3847; E-mail: Alan.Verkman@ucsf.edu
View this article at: http://www.jci.org/articles/view/67554?key=eb9bbcb11dc37e2fc635
Journal
Journal of Clinical Investigation