http://www.jci.org/just-published en-us 2009 The American Society for Clinical Investigation http://www.jci.org/icons/banner/rss_title.gif http://content.jci.org Michelle L. Gumz, Lisa R. Stow, I. Jeanette Lynch, Megan M. Greenlee, Alicia Rudin, Brian D. Cain, David R. Weaver, Charles S. Wingo http://www.jci.org/articles/view/36908 Per1) mRNA in renal collecting duct cell lines and in the rodent kidney. RNA silencing of Period 1 dramatically decreased expression of mRNA encoding αENaC in the presence or absence of aldosterone. Furthermore, expression of αENaC-encoding mRNA was attenuated in the renal medulla of mice with disruption of the Per1 gene, and these mice exhibited increased urinary sodium excretion. Renal αENaC-encoding mRNA was expressed in an apparent circadian pattern, and this pattern was dramatically altered in mice lacking functional Period genes. These results suggest a role for Period 1 in the regulation of the renal epithelial sodium channel and more broadly implicate the circadian clock in control of sodium balance. ]]> info:doi/10.1172/JCI36908 American Society for Clinical Investigation Jiangao Zhu, Xiaopei Huang, Yiping Yang http://www.jci.org/articles/view/37607 + T cell responses to both the transgene product and the AAV capsid, leading to loss of transgene expression and the generation of transgene product–specific and AAV-neutralizing antibodies. We further demonstrate that TLR9-dependent activation of adaptive immunity targeting AAV was mediated by type I IFNs and that human pDCs could be activated in vitro to induce type I IFN production via TLR9. These results reveal an essential role for the TLR9-MyD88–type I IFN pathway in induction of adaptive immune responses to AAV and suggest that strategies that interfere with this pathway may improve the outcome of AAV-mediated gene therapy in humans. ]]> info:doi/10.1172/JCI37607 American Society for Clinical Investigation Ainara Vallejo-Illarramendi, Keling Zang, Louis F. Reichardt http://www.jci.org/articles/view/38194 Wnt1cre, yielding craniofacial and cardiovascular malformations resembling those observed in individuals with DiGeorge syndrome. In these mice, we observed normal cardiac NCC migration but reduced differentiation into smooth muscle within the aortic arch arteries and impaired cardiac outflow tract rotation, which resulted in a dextroposed aortic root. Moreover, within the conotruncal cushions, Fak-deficient NCCs formed a less organized mesenchyme, with reduced expression of perlecan and semaphorin 3C, and exhibited disorganized F-actin stress fibers within the aorticopulmonary septum. Additionally, absence of Fak resulted in reduced in vivo phosphorylation of Crkl and Erk1/2, components of a signaling pathway essential for NCC development. Consistent with this, both TGF-β and FGF induced FAK and Crkl phosphorylation in control but not Fak-deficient NCCs in vitro. Our results indicate that FAK plays an essential role in cardiac outflow tract development by promoting the activation of molecules such as Crkl and Erk1/2. ]]> info:doi/10.1172/JCI38194 American Society for Clinical Investigation Julia Menke, Yasunori Iwata, Whitney A. Rabacal, Ranu Basu, Yee G. Yeung, Benjamin D. Humphreys, Takashi Wada, Andreas Schwarting, E. Richard Stanley, Vicki R. Kelley http://www.jci.org/articles/view/39087 + cells were genetically ablated and determined that macrophages only partially accounted for CSF-1–dependent tubular repair. We found that TECs expressed the CSF-1R and that this receptor was upregulated and coexpressed with CSF-1 in TECs following renal injury in mice and humans. Furthermore, signaling via the CSF-1R stimulated proliferation and reduced apoptosis in human and mouse TECs. Taken together, these data suggest that CSF-1 mediates renal repair by both a macrophage-dependent mechanism and direct autocrine/paracrine action on TECs. ]]> info:doi/10.1172/JCI39087 American Society for Clinical Investigation