A mouse model to evaluate potential age-promoting compounds
While there are well-established mouse models to identify cancer-causing agents, similar models are not available to readily test and identify age-promoting agents. Recently, a mouse strain (p16LUC mice) was developed that can be used to evaluate the transcription of p16INK4, which is increasingly expressed during aging and in age-associated diseases. In this issue of the Journal of Clinical Investigation, Norman Sharpless and colleagues at the University of North Carolina evaluated potential age-promoting compounds, including arsenic, a high-fat diet, UV light, and cigarette smoke in p16LUC mice. The authors found that a high fat diet did not accelerate p16INK4 expression, but both UV light exposure and cigarette smoke exposure dramatically increased p16INK4 expression compared to controls that had not been exposed to these age-promoting compounds. This study demonstrates that p16LUC mice are an appropriate model system for evaluating potetnail age-promoting compounds.
TITLE: p16INK4A- reporter mice reveal age-promoting effects of environmental toxicants
AUTHOR CONTACT: Norman E. Sharpless
UNC-Chapel Hill, Chapel Hill, NC, USA
Phone: 919.966.8212; E-mail: nes@med.unc.edu
View this article at: http://www.jci.org/articles/view/70960?key=d3965dabfff1a9a955b1
Hybrid protein deregulates complement in dense deposit disease
Dense deposit disease is a rare congenital disorder that is associated with complement dysfunction and often results in end stage renal disease within 10 years of the initial diagnosis. A small percentage of dense deposit disease is associated with mutations in the genes encoding factor H or C3 and autoantibody production. In this issue of the Journal of Clinical Investigation, Peter Zipfel and colleagues at the Leibniz Institute for Natural Products Research and Infection Biology, evaluated an index family that had 2 reported cases of dense deposit disease. The authors identified a chromosomal deletion in the complement factor H–related (CFHR) gene cluster that resulted in production of a hybrid CFHR2/CFRH5, which stabilized C3 convertase. Treatment with soluble C1 restored C3 convertase decay and may be a promising treatment for patients with a similar refractory form of dense despite disease.
TITLE: Complement factor H–related hybrid protein deregulates complement in dense deposit disease
AUTHOR CONTACT: Peter F Zipfel
Leibniz Institute for Natural Product Research and Infection Biology, Jena, , DEU
Phone: 49 3641 5321300; Fax: 49 3641 5320807; E-mail: peter.zipfel@hki-jena.de
View this article at: http://www.jci.org/articles/view/71866?key=83adcf2d94cecbc2b962
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AUTHOR CONTACT: H. Leighton Grimes
Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
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AUTHOR CONTACT: Corinne Linardic
Duke University, Durham, NC, USA
Phone: (919) 681-3709; Fax: (919) 681-6906; E-mail:linar001@mc.duke.edu
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TITLE: Nervous glucose sensing regulates postnatal β cell proliferation and glucose homeostasis
AUTHOR CONTACT: Bernard Thorens
University of Lausanne, Lausanne, , CHE
Phone: +41 21 692 3981; Fax: +41 21 692 3985; E-mail: bernard.thorens@unil.ch
View this article at: http://www.jci.org/articles/view/69154?key=6b2f4b5a245d96b3aa7f
TITLE: Carbon monoxide-based therapy ameliorates acute pancreatitis via TLR4 inhibition
AUTHOR CONTACT: Aida Habtezion
Stanford University, Stanford, CA, USA
Phone: 650-725-3362; E-mail: aidah@stanford.edu
View this article at: http://www.jci.org/articles/view/71362?key=db62bacdf4a18d58900f
TITLE: Pancreatic cancer-associated retinoblastoma 1 dysfunction enables TGF-β to promote proliferation
AUTHOR CONTACT: Murray Korc
Indiana University Medical School, Indianapolis, IN, USA
Phone: 3172786410; Fax: 317-274-8046; E-mail: mkorc@iu.edu
View this article at: http://www.jci.org/articles/view/71526?key=1116c32e0f4e94abbd75
TITLE: Lysosomal β-glucuronidase regulates Lyme and rheumatoid arthritis severity
AUTHOR CONTACT: Janis Weis
University of Utah School of Medicine, Salt Lake City, UT, USA
Phone: 801 581-8386; Fax: 801-585-2417; E-mail: janis.weis@path.utah.edu
View this article at: http://www.jci.org/articles/view/72339?key=075142ed8f86221102fc
Journal
Journal of Clinical Investigation