Since the first example of conditional gene targeting in mice in 1994, the use of Cre recombinase and loxP flanked sequences has become an invaluable technique to generate tissue and temporal specific gene knockouts. The number of mouse strains expressing floxed-gene sequences, and tissue-specific or temporal-specific Cre-recombinase that have been reported in the literature has grown exponentially. However, increased use of this technology has highlighted several problems that can impact the interpretation of any phenotype observed in these mouse models. In particular, accurate knowledge of the specificity of Cre expression in each strain is critical in order to make conclusions about the role of specific cell types in the phenotypes observed. Cre-mediated deletion specificity and efficiency has been described in many different ways in the literature, making direct comparisons between these Cre strains impossible. Here we report crossing thirteen different myeloid-Cre mouse strains to ROSA-EYFP reporter mice and assaying YFP expression in a variety of naïve unstimulated hematopoietic cells, in parallel. By focusing on myeloid subsets, we directly compare the relative efficiency and specificity of myeloid deletion in these strains under steady-state conditions.

Summary The motheaten mouse has long served as a paradigm for complex autoimmune and inflammatory disease. Null mutations in Ptpn6, which encodes the non-receptor protein-tyrosine phosphatase Shp1, cause the motheaten phenotype. However, Shp1 regulates multiple signaling pathways in different hematopoietic cell types, so the cellular and molecular mechanism of autoimmunity and inflammation in the motheaten mouse has remained unclear. Using floxed Ptpn6 mice, we dissected the contribution of innate immune cells to the motheaten phenotype. Ptpn6 deletion in neutrophils resulted in cutaneous inflammation but not autoimmunity, providing an animal model of human neutrophilic dermatoses. By contrast, dendritic cell deletion caused severe autoimmunity, without inflammation. Genetic and biochemical analysis showed that inflammation was caused by enhanced neutrophil integrin signaling through Src-family and Syk kinases, whereas autoimmunity resulted from exaggerated MyD88-dependent signaling in dendritic cells. Our data demonstrate that disruption of distinct Shp1-regulated pathways in different cell types combine to cause motheaten disease.

A five-level reporting system for prostate cancer pathology is associated with the risk of late prostate cancer endpoints.

Tranexamic acid (TXA) has been used to manage menstrual bleeding and reduce bleeding during orthopedic procedures, but has not been widely used in urology. We present a patient with refractory gross hematuria with required therapeutic anticoagulation who failed multiple other measures to control prostatic bleeding. This patient's hematuria abated with endoscopic localized injection of tranexamic acid into the prostate. The effects were durable with no bleeding recurrence reported while maintaining therapeutic anticoagulation.