demonstrate the functional importance of Sp1 in vivo using our mouse model for PHPV. Regrettably, Sp12/2 mice display an embryonic lethal phenotype at E11.5, before primary vitreous development. 17429684 Tissue specific Sp1 knockout using a Wnt1-Cre driver would be very informative. Finally, we have carried out this line of investigation in the mouse to gain insight into human diseases, like cancer and PHPV. Repression of human ARF expression is a relatively common mechanism by which cancers can evade this tumor suppressor activity; presumably, restoring ARF expression could represent a novel therapeutic approach, especially for that subset of cancers also retaining wild type p53. As a human disease, PHPV is typically sporadic, but several reports of familial disease suggest that it could have an underlying genetic basis. C/ebpb is frequently expressed in human cancer and has been implicated as an oncogenic factor or tumor suppressor with the capacity to foster senescence. These disparate effects may be due, in part, to the capacity of C/ebpb to form homo- and heterodimeric complexes with either activating or transcriptional repressive activity. Sp1, too, could act as a Tgfb-dependent tumor suppressor, by controlling Ink4b or Arf, or as an oncogene by facilitating EMT. Again, one could envision that the net effect of Sp1 could depend on the underlying cellular or genetic context. As more sophisticated, “next-generation”genome sequencing and analytical tools are applied particularly to diseases like PHPV the role for these genes might be revealed. Acknowledgments We gratefully acknowledge 
Syann Lee and Joel Elmquist for assistance with LCM. We thank other members of the Skapek lab for technical assistance and helpful discussion. Hemolytic uremic syndrome is purchase Varlitinib characterized by nonimmune hemolytic anemia, thrombocytopenia and acute renal failure. The classical form of HUS is a complication of Shiga toxin -producing Escherichia coli infection, the most prevalent infectious agent responsible for the development of this pathology. In Argentina, HUS is endemic with a high incidence of more than 500 cases per year, being the most common cause of acute renal failure and the second leading cause of chronic renal failure in children younger than 5 years old. Clinical and histological renal damage has been strongly associated with Stx types 1 and 2 produced by O157:H7 STEC, although strains that only express Stx2 are highly prevalent in Argentina. However, other non-O157:H7 serotypes have been shown to cause HUS. STEC are present in the intestinal tract of healthy cattle and disease outbreaks are frequently due to ingestion of undercooked ground beef, manure-contaminated water, vegetables, fruit or unpasteurized milk. After bacteria colonize the bowel, Stx is released into the gut lumen and then absorbed into the circulation, where the toxin reaches vascular endothelial cells and finally binds its specific receptor, the globotriaosylceramide . This receptor is located on the plasma membrane of target cells, particularly microvascular endothelial cells present in the kidneys, brain and other organs. Nevertheless the human kidney is the most affected organ in diarrhea-associated HUS, the likely reason being the presence of very Stx-sensitive cells which express 1 Stx2 and SubAB action on human microvasculature high amounts of biologically active Stx receptor. Indeed, human microvascular endothelial cells express 50-fold higher 1717682 Gb3 levels than endothelial cell