Spontaneous Development of Cutaneous Squamous Cell Carcinoma in Mice with Cell-specific Deletion of Inhibitor of κB Kinase 2.

The deletion of NFκB in epithelial tissues by using skin-specific promoters can cause both tumor formation and severe inflammatory dermatitis, indicating that this signaling pathway is important for the maintenance of immune homeostasis in epithelial tissues. In the present study, we crossed mice transgenic for loxP-Ikbk2 and human Gfap-cre to selectively delete IKK2 in CNS astrocytes. Unexpectedly, a subset of mice developed severe and progressive skin lesions marked by hyperplasia, hyperkeratosis, dysplasia, inflammation, and neoplasia with a subset of lesions diagnosed as squamous cell carcinoma (SCC). The development of lesions was monitored over a 3.5-y period and over 4 filial generations. Average age of onset of was 4 mo of age with 19.5% of mice affected with frequency increasing in progressive generations. Lesion development appeared to correlate not only with unintended IKK2 deletion in GFAP expressing cells of the epidermis, but also with increased expression of TNF in lesioned skin. The skins changes described in these animals are similar to those in transgenic mice with an epidermis-specific deletion of NFκB and thus represents another genetic mouse model that can be used to study the role of NFκB signaling in regulating the development of SCC.

Comparison of 3 real-time, quantitative murine models of staphylococcal biofilm infection by using in vivo bioluminescent imaging.

Biofilm formation represents a unique mechanism by which Staphylococcus aureus and other microorganisms avoid antimicrobial clearance and establish chronic infections. Treatment of these infections can be challenging, because the bacteria in the biofilm state are often resistant to therapies that are effective against planktonic bacteria of the same species. Effective animal models for the study of biofilm infections and novel therapeutics are needed. In addition, there is substantial interest in the use of noninvasive, in vivo data collection techniques to decrease the animal numbers required for the execution of infectious disease studies. To ad- dress these needs, we evaluated 3 murine models of implant-associated biofilm infection by using in vivo bioluminescent imaging techniques. The goal of these studies was to identify the model that was most amenable to development of sustained infections that could be imaged repeatedly in vivo by using bioluminescent technology. We found that the subcutaneous mesh and tibial intramedullary pin models both maintained consistent levels of bioluminescence for as long as 35 d after infection, with no implant loss experienced in either model. In contrast, a subcutaneous catheter model demonstrated significant incidence of incisional ab- scessation and implant loss by day 20 after infection. The correlation of bioluminescent measurements and bacterial enumeration was strongest with the subcutaneous mesh model. Among the 3 models we evaluated, the subcutaneous mesh model is the most appropriate animal model for prolonged study of biofilm infections by using bioluminescent imaging.

Transabdominal ultrasound for pregnancy diagnosis in Reeves' muntjac deer.

Reeves' muntjac deer (Muntiacus reevesi) are a small cervid species native to southeast Asia, and are currently being investigated as a potential model of prion disease transmission and pathogenesis. Vertical transmission is an area of interest among researchers studying infectious diseases, including prion disease, and these investigations require efficient methods for evaluating the effects of maternal infection on reproductive performance. Ultrasonographic examination is a well-established tool for diagnosing pregnancy and assessing fetal health in many animal species(1-7), including several species of farmed cervids(8-19), however this technique has not been described in Reeves' muntjac deer. Here we describe the application of transabdominal ultrasound to detect pregnancy in muntjac does and to evaluate fetal growth and development throughout the gestational period. Using this procedure, pregnant animals were identified as early as 35 days following doe-buck pairing and this was an effective means to safely monitor the pregnancy at regular intervals. Future goals of this work will include establishing normal fetal measurement references for estimation of gestational age, determining sensitivity and specificity of the technique for diagnosing pregnancy at various stages of gestation, and identifying variations in fetal growth and development under different experimental conditions.