Quantitative tomography of early-onset spontaneous AA amyloidosis in interleukin 6 transgenic mice.

Mice that constitutively express the human interleukin 6 (huIL6) protein from a heritable transgene (H2-L(d)-IL-6) express high levels of the acute-phase reactant, serum amyloid protein A, a liver-derived apoprotein of high-density lipoprotein that is the precursor of AA amyloid. Typically at approximately 5 mo of age B6(C)- Tg(H2-L(d)-IL-6)Kish (H2/huIL-6) animals begin to develop splenic deposits of AA amyloid, which progress to involve the liver, kidney, and vasculature, ultimately resulting in death due to severe systemic AA amyloidosis at 8 to 9 mo of age. These mice provide a robust model in which to study novel therapeutic and diagnostic imaging agents for AA amyloidosis. We recently have noted a change in onset of spontaneous disease, as evidenced by 2 female transgenic mice that were found moribund at only 5 mo of age. Extensive hepatosplenic amyloid deposits in both mice were identified and quantified by single-photon emission computed tomography, which further revealed heterogeneous distribution of radiotracer in the spleen indicating a distinction between amyloid-laden red pulp and the disease-free lymphoid follicles. The AA nature of the deposits was evidenced immunohistochemically and by mass spectrometric analyses of extracted amyloid fibrils. Our studies have documented the manifestation of early-onset, severe, spontaneous AA amyloidosis in 2- to 5-mo-old H2/ huIL-6 mice; we hypothesize that this disease is due to genetic rather than environmental factors.

An AOTF-based dual-modality hyperspectral imaging system (DMHSI) capable of simultaneous fluorescence and reflectance imaging.

An acousto-optic tunable filter (AOTF)-based system for dual-modality hyperspectral imaging (DMHSI) has been developed for use in characterization of normal and malignant mouse tissue. The system consists of a laser, endoscope, AOTF, and two cameras coupled with optics and electronics. Initial results show that the system can delineate normal and malignant mouse tissues real-time. The analysis shows that malignant tissues consistently exhibit less fluorescent intensity in the wavelength band from 440 to 540 nm with a peak intensity of around 490 nm. The analysis also shows key spectroscopic differences between normal and malignant tissues. Further, these results are compared to real-time spectroscopic data and show good correlation.

Genomes to Life "Center for Molecular and Cellular Systems": a research program for identification and characterization of protein complexes.

Goal 1 of Department of Energy's Genomes to Life (GTL) program seeks to identify and characterize the complete set of protein complexes within a cell. Goal 1 forms the foundation necessary to accomplish the other objectives of the GTL program, which focus on gene regulatory networks and molecular level characterization of interactions in microbial communities. Together this information would allow cells and their components to be understood in sufficient detail to predict, test and understand the responses of a biological system to its environment. The Center for Molecular and Cellular Systems has been established to identify and characterize protein complexes using high through-put analytical technologies.A dynamic research program is being developed that supports the goals of the Center by focusing on the development new capabilities for sample preparation and complex separations, molecular level identification of the protein complexes by mass spectrometry, characterization of the complexes in living cells by imaging techniques, and bioinformatics and computational tools for the collection and interpretation of data and formation of databases and tools to allow the data to be shared by the biological community.