ap20187 and Disease-Models--Animal

Acute kidney injury (AKI) is a major cause of patient mortality and a major risk multiplier for the progression to chronic kidney disease (CKD). The mechanism of the AKI to CKD transition is complex but is likely mediated by the extent and length of the inflammatory response following the initial injury. Lymphatic vessels help to maintain tissue homeostasis through fluid, macromolecule, and immune modulation. Increased lymphatic growth, or lymphangiogenesis, often occurs during inflammation and plays a role in acute and chronic disease processes. What roles renal lymphatics and lymphangiogenesis play in AKI recovery and CKD progression remains largely unknown. To determine if the increased lymphatic density is protective in the response to kidney injury, we utilized a transgenic mouse model with inducible, kidney-specific overexpression of the lymphangiogenic protein vascular endothelial growth factor-D to expand renal lymphatics. "KidVD" mouse kidneys were injured using inducible podocyte apoptosis and proteinuria (POD-ATTAC) or bilateral ischemia reperfusion. In the acute injury phase of both models, KidVD mice demonstrated a similar loss of function measured by serum creatinine and glomerular filtration rate compared to their littermates. While the initial inflammatory response was similar, KidVD mice demonstrated a shift toward more CD4+ and fewer CD8+ T cells in the kidney. Reduced collagen deposition and improved functional recovery over time was also identified in KidVD mice. In KidVD-POD-ATTAC mice, an increased number of podocytes were counted at 28 days post-injury. These data demonstrate that increased lymphatic density prior to injury alters the injury recovery response and affords protection from CKD progression.

Topics: Acute Kidney Injury; Animals; Apoptosis; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Collagen; Disease Models, Animal; Kidney; Lymphangiogenesis; Lymphatic Vessels; Mice; Mice, Transgenic; Podocytes; Proteinuria; Recovery of Function; Reperfusion Injury; Tacrolimus; Vascular Endothelial Growth Factor D

Attenuating pathological angiogenesis in diseases characterized by neovascularization such as diabetic retinopathy has transformed standards of care. Yet little is known about the molecular signatures discriminating physiological blood vessels from their diseased counterparts, leading to off-target effects of therapy. We demonstrate that in contrast to healthy blood vessels, pathological vessels engage pathways of cellular senescence. Senescent (p16

Topics: Animals; Apoptosis; bcl-X Protein; Cellular Senescence; Collagen Type I, alpha 1 Chain; Cyclin-Dependent Kinase Inhibitor p16; Disease Models, Animal; Endothelial Cells; Female; Flavonols; Humans; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Neovascularization, Pathologic; Retinal Diseases; Tacrolimus

For scientists working within the field of induced pluripotent stem cells (iPSCs), this protocol will provide a thorough walk-through on how to conduct in vitro and in vivo experiments that validate the function of a particular safeguard system technology. In short, we provide instructions on how to generate inducible Caspase-9 (iC9) safeguard system with human iPSCs that act as normal or abnormal models of the cells for therapeutics to be tried after differentiation. These iC9-iPSCs should be modified prior to beginning this protocol by constitutively expressing luciferase, an enzyme capable of generating bioluminescent signals through the oxidation of the substrate luciferin. Monitoring the bioluminescent signal over time provides the information on whether a safeguard system is working or not.

Topics: Animals; Benzothiazoles; Caspase 9; Cell Culture Techniques; Cell Differentiation; Cell Line; Culture Media; Disease Models, Animal; Gene Expression; Genes, Reporter; Genes, Transgenic, Suicide; Humans; Immunotherapy; Induced Pluripotent Stem Cells; Injections, Intraperitoneal; Intravital Microscopy; Luciferases, Firefly; Luminescent Measurements; Mice, Inbred NOD; Mice, SCID; Tacrolimus; Teratoma; Tumor Burden

Cellular senescence entails a stable cell-cycle arrest and a pro-inflammatory secretory phenotype, which contributes to aging and age-related diseases. Obesity is associated with increased senescent cell burden and neuropsychiatric disorders, including anxiety and depression. To investigate the role of senescence in obesity-related neuropsychiatric dysfunction, we used the INK-ATTAC mouse model, from which p16

Topics: Animals; Anxiety; Astrocytes; Behavior, Animal; Brain; Cells, Cultured; Cellular Senescence; Cyclin-Dependent Kinase Inhibitor p16; Dasatinib; Diet, High-Fat; Disease Models, Animal; Female; Fibroblasts; Lipid Droplets; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Neurogenesis; Obesity; Quercetin; Tacrolimus

Formation of 43S and 48S preinitiation complexes plays an important role in muscle protein synthesis. There is no muscle-wasting mouse model caused by a repressed 43S preinitiation complex assembly.. The aim of the present study was to develop a convenient mouse model of skeletal muscle wasting with repressed 43S preinitiation complex assembly.. A ligand-activatable PERK derivative Fv2E-PERK causes the phosphorylation of eukaryotic initiation factor 2α (eIF2α), which inhibits 43S preinitiation complex assembly. Thus, muscle atrophic phenotypes, intracellular signaling pathways, and intracellular free amino acid profiles were investigated in human skeletal muscle α-actin (HSA) promoter-driven Fv2E-PERK transgenic (Tg) mice.. HSA-Fv2E-PERK Tg mice treated with the artificial dimerizer AP20187 phosphorylates eIF2α in skeletal muscles and leads to severe muscle atrophy within a few days of ligand injection. Muscle atrophy was accompanied by a counter regulatory activation of mTORC1 signaling. Moreover, intracellular free amino acid levels were distinctively altered in the skeletal muscles of HSA-Fv2E-PERK Tg mice.. As a novel model of muscle wasting, HSA-Fv2E-PERK Tg mice provide a convenient tool for studying the pathogenesis of muscle loss and for assessing putative therapeutics.

Topics: Actins; Amino Acids; Animals; Disease Models, Animal; eIF-2 Kinase; Homeostasis; Humans; Intracellular Space; Ligands; Mechanistic Target of Rapamycin Complex 1; Mice, Inbred C57BL; Mice, Transgenic; Multiprotein Complexes; Muscle, Skeletal; Muscular Atrophy; Promoter Regions, Genetic; Protein Serine-Threonine Kinases; Tacrolimus; TOR Serine-Threonine Kinases

Herpes simplex virus type-1 (HSV-1) is a leading cause of neurotrophic keratitis, characterized by decreased or absent corneal sensation due to damage to the sensory corneal innervation. We previously reported the elicited immune response to infection contributes to the mechanism of corneal nerve regression/damage during acute HSV-1 infection. Our aim is to further establish the involvement of infiltrated macrophages in the mechanism of nerve loss upon infection.. Macrophage Fas-Induced Apoptosis (MAFIA) transgenic C57BL/6 mice were systemically treated with AP20187 dimerizer or vehicle (VEH), and their corneas, lymph nodes, and blood were assessed for CD45+CD11b+GFP+ cell depletion by flow cytometry (FC). Mice were ocularly infected with HSV-1 or left uninfected. At 2, 4, and/or 6 days post infection (PI), corneas were assessed for sensitivity and harvested for FC, nerve structure by immunohistochemistry, viral content by plaque assay, soluble factor content by suspension array, and activation of signaling pathways by Western blot analysis. C57BL6 mice were used to compare to the MAFIA mouse model.. MAFIA mice treated with AP20187 had efficient depletion of CD45+CD11b+GFP+ cells in the tissues analyzed. The reduction of CD45+CD11b+GFP+ cells recruited to the infected corneas of AP20187-treated mice correlated with preservation of corneal nerve structure and function, decreased protein concentration of inflammatory cytokines, and decreased STAT3 activation despite no changes in viral content in the cornea compared to VEH-treated animals.. Our results suggest infiltrated macrophages are early effectors in the nerve regression following HSV-1 infection. We propose the neurodegeneration mechanism involves macrophages, local up-regulation of IL-6, and activation of STAT3.

Topics: Animals; Blotting, Western; Cornea; Disease Models, Animal; Flow Cytometry; Herpesvirus 1, Human; Immunohistochemistry; Interleukin-6; Keratitis, Herpetic; Macrophages; Mice; Mice, Inbred C57BL; Mice, Transgenic; Nerve Degeneration; Receptor, Macrophage Colony-Stimulating Factor; STAT3 Transcription Factor; Tacrolimus; Trigeminal Nerve; Trigeminal Nerve Diseases; Viral Plaque Assay

Pulmonary arterial hypertension (PAH) is a lethal disease that is characterized by functional and structural abnormalities involving distal pulmonary arterioles that result in increased pulmonary vascular resistance and ultimately right heart failure. In experimental models of pulmonary hypertension, endothelial cell (EC) apoptosis is a necessary trigger for the development of obliterative lung arteriopathy, inducing the emergence of hyperproliferative and apoptosis-resistant vascular cells. However, it has not been established whether EC apoptosis is sufficient for the induction of complex lung arteriolar lesions. We generated a conditional transgenic system in mice to test the hypothesis that lung endothelial cell apoptosis is sufficient to induce a PAH phenotype. The Fas-induced apoptosis (FIA) construct was expressed under the control of endothelial-specific Tie2 promoter (i.e., EFIA mice), and administration of a small molecule dimerizing agent, AP20187, resulted in modest pulmonary hypertension, which was associated with obliterative vascular lesions localized to distal lung arterioles in a proportion of transgenic mice. These lesions were characterized by proliferating cells, predominantly CD68 macrophages. Although endothelial cell apoptosis was also seen in the kidney, evidence of subsequent arteriopathy was seen only in the lung. This model provides direct evidence that lung endothelial cell apoptosis acts as a trigger to initiate a PAH phenotype and provides initial insight into the potential mechanisms that underlie a lung-specific arterial response to endothelial injury.

Topics: Animals; Apoptosis; Disease Models, Animal; fas Receptor; Fas-Associated Death Domain Protein; Gene Expression Regulation; Hypertension, Pulmonary; Lung; Mice; Mice, Transgenic; Plasmids; Promoter Regions, Genetic; Protein Multimerization; Pulmonary Artery; Receptor, TIE-2; Recombinant Fusion Proteins; Respiratory Mucosa; Signal Transduction; Tacrolimus; Tacrolimus Binding Proteins; Transfection

We previously reported a transgenic Xenopus laevis model of retinitis pigmentosa in which tadpoles express the bovine form of P23H rhodopsin (bP23H) in rod photoreceptors. In this model, retinal degeneration was dependent on light exposure. Here, we investigated ultrastructural changes that occurred in the rod photoreceptors of these retinas when exposed to light.. Tadpoles expressing bP23H in rods were transferred from constant darkness to a 12-hour light:12-hour dark (12L:12D) regimen. For comparison, transgenic tadpoles expressing an inducible form of caspase 9 (iCasp9) were reared in a 12L:12D regimen, and retinal degeneration was induced by administration of the drug AP20187. Tadpoles were euthanized at various time points, and eyes were processed for confocal light and transmission electron microscopy.. We observed defects in outer and inner segments of rods expressing bP23H that were aggravated by light exposure. Rod outer segments exhibited vesiculations throughout and were rapidly phagocytosed by the retinal pigment epithelium. In rod inner segments, we observed autophagic compartments adjacent to the endoplasmic reticulum and extensive vesiculation at later time points. These defects were not found in rods expressing iCasp9, which completely degenerated within 36 hours after drug administration.. Our results indicate that ultrastructural defects in outer and inner segment membranes of bP23H expressing rods differ from those observed in drug-induced apoptosis. We suggest that light-induced retinal degeneration caused by P23H rhodopsin occurs via cell death with autophagy, which may represent an attempt to eliminate the mutant rhodopsin and/or damaged cellular compartments from the secretory pathway.

Topics: Animals; Animals, Genetically Modified; Autophagy; Caspase 9; Disease Models, Animal; Light; Photoperiod; Radiation Injuries, Experimental; Retinal Photoreceptor Cell Inner Segment; Retinal Rod Photoreceptor Cells; Retinitis Pigmentosa; Rhodopsin; Rod Cell Outer Segment; Tacrolimus; Xenopus laevis

There is compelling evidence that oligodendrocyte apoptosis, in response to CNS inflammation, contributes significantly to the development of the demyelinating disorder multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). Therefore, approaches designed to protect oligodendrocytes would likely have therapeutic value. Activation of pancreatic endoplasmic reticulum kinase (PERK) signaling in response to endoplasmic reticulum (ER) stress increases cell survival under various cytotoxic conditions. Moreover, there is evidence that PERK signaling is activated in oligodendrocytes within demyelinating lesions in multiple sclerosis and EAE. Our previous study demonstrated that CNS delivery of the inflammatory cytokine interferon-γ before EAE onset protected mice against EAE, and this protection was dependent on PERK signaling. In our current study, we sought to elucidate the role of PERK signaling in oligodendrocytes during EAE. We generated transgenic mice that allow for temporally controlled activation of PERK signaling, in the absence of ER stress, specifically in oligodendrocytes. We demonstrated that persistent activation of PERK signaling was not deleterious to oligodendrocyte viability or the myelin of adult animals. Importantly, we found that enhanced activation of PERK signaling specifically in oligodendrocytes significantly attenuated EAE disease severity, which was associated with reduced oligodendrocyte apoptosis, demyelination, and axonal degeneration. This effect was not the result of an altered degree of the inflammatory response in EAE mice. Our results provide direct evidence that activation of PERK signaling in oligodendrocytes is cytoprotective, protecting mice against EAE.

Topics: Age Factors; Animals; Animals, Newborn; Brain; Bromodeoxyuridine; Cell Proliferation; Cells, Cultured; Cytokines; Disease Models, Animal; eIF-2 Kinase; Encephalomyelitis, Autoimmune, Experimental; Female; Gene Expression Regulation; Immunosuppressive Agents; In Situ Nick-End Labeling; Mice; Mice, Transgenic; Microscopy, Electron, Transmission; Myelin Basic Protein; Myelin Proteolipid Protein; Neutrophil Infiltration; Oligodendroglia; Protein Phosphatase 1; Receptor Protein-Tyrosine Kinases; RNA, Messenger; Signal Transduction; Stem Cells; T-Lymphocytes; Tacrolimus; Time Factors; Transcription Factor CHOP

Goldmann-Favre syndrome, also known as enhanced S-cone syndrome, is an inherited retinal degeneration disease in which a gain of photoreceptor cell types results in retinal dysplasia and degeneration. Although microglia have been implicated in the pathogenesis of many neurodegenerative diseases, the fundamental role of these cells in this disease is unknown. In the current study, sequential analyses suggest that microglia are recruited and appear after outer nuclear layer folding. By crossing rd7 mice (a model for hereditary retinal degeneration owing to Nr2e3 mutation) with mice carrying the macrophage Fas-induced apoptosis (Mafia) transgene, we generated double-mutant mice and studied the role of the resident retinal microglia. Microglial cells in these double-mutant mice express enhanced green fluorescent protein (EGFP) and a suicide gene that can trigger Fas-mediated apoptosis via systemic treatment with AP20187 (FK506 dimerizer). We demonstrated that more than 80% of the EGFP+ cells in retinas from rd7/rd7;Tg/Tg mice express Iba-1 (a microglial marker), and resident microglia are still present in the retina because AP20187 does not cross the blood-brain barrier. Hence, only circulating bone marrow (BM)-derived microglia are depleted. Depletion of circulating BM-derived microglia accelerates retinal degeneration in rd7 mice. An increased number of autofluorescent (AF) spots is a consequence of resident microglia proliferation, which in turn establishes an inflammatory cytokine milieu via the upregulation of IL-1β, IL-6 and TNFα expression. This inflammation is likely to accelerate retinal degeneration. This study not only identifies inflammation as a crucial step in the pathogenesis of retinal degeneration, but also highlights the involvement of specific cytokine genes that could serve as future treatment targets in retinal degenerations.

Topics: Animals; Bone Marrow Cells; Cell Count; Cell Proliferation; Disease Models, Animal; Eye Diseases, Hereditary; Fluorescein Angiography; Gene Expression Regulation; Green Fluorescent Proteins; Immunohistochemistry; Mice; Mice, Inbred C57BL; Mice, Transgenic; Microglia; Retinal Degeneration; Rod Cell Outer Segment; Tacrolimus; Time Factors; Vision Disorders

Most degenerative diseases begin with a gradual loss of specific cell types before reaching a threshold for symptomatic onset. However, the endogenous regenerative capacities of different tissues are difficult to study, because of the limitations of models for early stages of cell loss. Therefore, we generated a transgenic mouse line (Mos-iCsp3) in which a lox-mismatched Cre/lox cassette can be activated to produce a drug-regulated dimerizable caspase-3. Tissue-restricted Cre expression yielded stochastic Casp3 expression, randomly ablating a subset of specific cell types in a defined domain. The limited and mosaic cell loss led to distinct responses in 3 different tissues targeted using respective Cre mice: reversible, impaired glucose tolerance with normoglycemia in pancreatic β cells; wound healing and irreversible hair loss in the skin; and permanent moderate deafness due to the loss of auditory hair cells in the inner ear. These mice will be important for assessing the repair capacities of tissues and the potential effectiveness of new regenerative therapies.

Topics: Alopecia; Animals; Apoptosis; Caspase 3; Cell Lineage; Dimerization; Disease Models, Animal; Epidermis; Gene Expression Regulation; Gene Knockdown Techniques; Genes, Transgenic, Suicide; Glucose Intolerance; Hair Cells, Auditory, Inner; Hearing Loss, Bilateral; Hearing Loss, Sensorineural; Homeodomain Proteins; Insulin; Islets of Langerhans; Keratin-14; Mice; Mice, Inbred C57BL; Mice, Transgenic; Mosaicism; Organ Specificity; Phenotype; Tacrolimus; Transcription Factor Brn-3C; Transgenes; Wound Healing

Intranasal application of vesicular stomatitis virus (VSV) induces acute encephalitis characterized by a pronounced myeloid and T cell infiltrate. The role of distinct phagocytic populations on VSV encephalitis was therefore examined in this study. Ablation of peripheral macrophages did not impair VSV encephalitis or viral clearance from the brain, whereas, depletion of splenic marginal dendritic cells impaired this response and enhanced morbidity/mortality. Selective depletion of brain perivascular macrophages also suppressed this response without altering viral clearance. Thus, two anatomically distinct phagocytic populations regulate VSV encephalitis in a non-redundant fashion although neither population is essential for viral clearance in the CNS.

Topics: Animals; Apoptosis; Bone Density Conservation Agents; Central Nervous System; Clodronic Acid; Disease Models, Animal; Encephalitis, Viral; Flow Cytometry; Granulocytes; Green Fluorescent Proteins; Macrophages; Mice; Mice, Nude; Mice, Transgenic; Peritoneum; Tacrolimus; Vesiculovirus

Because of their high cone/rod ratio, Xenopus laevis may be a useful system for examining rod-cone interactions during retinal degeneration and mechanisms that underlie secondary cone degeneration. The authors developed an inducible model of retinitis pigmentosa (RP) in X. laevis to investigate these issues.. The authors generated transgenic X. laevis that express a modified caspase-9 (iCasp9) under the control of the X. laevis rod opsin promoter. iCasp9 is activated by the compound AP20187, resulting in an apoptotic cascade. Confocal microscopy, Western blot analysis, and electroretinography (ERG) were used to determine the effects of AP20187 on transgenic retinas.. AP20187 induced rod cell apoptosis in transgenic tadpoles and postmetamorphic frogs. Longitudinal results indicate rod cell death led to cone cell dysfunction within 3 months; however, cone function was reinstated after 6 months. Returning cone function may be associated with increased numbers of morphologically normal cone cells and thickening of the inner nuclear layer.. These studies indicate that X. laevis may be a useful system for examining cone dysfunction associated with rod death in RP and longer term regeneration of cone responses. This inducible model of RP is unique in that rod death proceeds through a well-understood mechanism, rod death can be carefully controlled to occur at any stage of development, and the stimulus for rod death can be removed at any time.

Topics: Animals; Animals, Genetically Modified; Apoptosis; Blotting, Western; Caspase 9; Disease Models, Animal; Electroretinography; Enzyme Activation; Gene Expression Regulation, Enzymologic; Green Fluorescent Proteins; Microscopy, Confocal; Opsins; Promoter Regions, Genetic; Retina; Retinal Cone Photoreceptor Cells; Retinal Rod Photoreceptor Cells; Retinitis Pigmentosa; Tacrolimus; Xenopus laevis

Islet transplantations have been performed clinically, but their practical applications are limited. An extensive effort has been made toward the identification of pancreatic beta-cell stem cells that has yielded many insights to date, yet targeted reconstitution of beta-cell mass remains elusive. Here, we present a mouse model for inducible and reversible ablation of pancreatic beta-cells named the PANIC-ATTAC (pancreatic islet beta-cell apoptosis through targeted activation of caspase 8) mouse.. We efficiently induce beta-cell death through apoptosis and concomitant hyperglycemia by administration of a chemical dimerizer to the transgenic mice. In contrast to animals administered streptozotocin, the diabetes phenotype and beta-cell loss are fully reversible in the PANIC-ATTAC mice, and we find significant beta-cell recovery with normalization of glucose levels after 2 months.. The rate of recovery can be enhanced by various pharmacological interventions with agents acting on the glucagon-like peptide 1 axis and agonists of peroxisome proliferator-activated receptor-gamma. During recovery, we find an increased population of GLUT2(+)/insulin(-) cells in the islets of PANIC-ATTAC mice, which may represent a novel pool of potential beta-cell precursors.. The PANIC-ATTAC mouse may be used as an animal model of inducible and reversible beta-cell ablation and therefore has applications in many areas of diabetes research that include identification of beta-cell precursors, evaluation of glucotoxicity effects in diabetes, and examination of pharmacological interventions.

Topics: Animals; Apoptosis; Caspase 8; Caspases; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Exenatide; Glucose Tolerance Test; Insulin-Secreting Cells; Male; Mice; Mice, Transgenic; Peptides; Reverse Transcriptase Polymerase Chain Reaction; Tacrolimus; Tacrolimus Binding Proteins; Transgenes; Venoms

We present a new mouse model for the study of peritoneal adhesions using macrophage Fas-induced apoptosis (Mafia) transgenic mice expressing a Fas-FKBP construct under control of the murine c-fms promoter. Mafia mice allow systemic macrophage depletion by dimerization of Fas with a synthetic dimerizer, AP20187. Results demonstrate that macrophage depletion in Mafia mice induces peritoneal adhesion formation when the peritoneal cavity is also exposed to an irritant. The Mafia mouse model presents a reproducible, non-surgical approach for research in adhesion formation and prevention.. Mafia mice were treated with AP20187 using an intravenous (i.v.) or intraperitoneal (i.p.) injection. Control groups included mock-treated Mafia mice and both AP20187 and mock-treated wild type mice. Seven days after treatment, mice were observed for the presence of adhesions.. After i.p. injection with AP20187, 76% of Mafia mice developed adhesions whereas none of the mock-treated Mafia or wild-type mice developed adhesions, and only one AP20187-treated wild-type mouse (5.8%) developed a mild adhesion. Mafia mice treated with AP20187 i.v. exhibited macrophage depletion not significantly different than i.p. treated mice, but did not develop adhesions. In contrast, Mafia mice treated with AP20187 i.v. developed adhesions when diluent was also injected into the peritoneal cavity, whereas i.p diluent alone had no effect.. Macrophage depletion, combined with a peritoneal irritant, results in peritoneal adhesion formation in transgenic Mafia mice. Macrophages appear to play a protective role in the development and/or repair of peritoneal adhesions.

Topics: Animals; Apoptosis; Disease Models, Animal; Fas Ligand Protein; Genes, fms; Macrophages; Membrane Glycoproteins; Mice; Mice, Inbred C57BL; Mice, Transgenic; Peritoneal Diseases; Tacrolimus; Tissue Adhesions; Tumor Necrosis Factors

Transgenic mice expressing an inducible suicide gene, which allows systemic and reversible elimination of macrophages, were developed. A macrophage-specific c-fms promoter was used to express enhanced green fluorescent protein and a drug-inducible suicide gene that leads to Fas-mediated apoptosis in resting and cycling cells of the macrophage lineage. Transgenic mice were fertile, of normal weight, and showed no abnormal phenotype before drug exposure. The transgene was expressed constitutively in macrophages and dendritic cells (DC) but not significantly in T cells or B cells. Induction of the suicide gene led to depletion of 70-95% of macrophages and DC in nearly all tissues examined. Depletion reduced the ability to clear bacteria from the blood and led to increased bacterial growth in the liver. Depleted mice displayed several abnormalities, including splenomegaly, lymphadenopathy, thymic atrophy, extramedullary hematopoiesis, and development of peritoneal adhesions. This new, transgenic line will be useful in investigating the role of macrophages and DC.

Topics: Animals; Apoptosis; Bacterial Infections; Cell Count; Cells, Cultured; Dendritic Cells; Dimerization; Disease Models, Animal; fas Receptor; Genes, Transgenic, Suicide; Green Fluorescent Proteins; Immunity, Cellular; Luminescent Proteins; Macrophages; Mice; Mice, Inbred C57BL; Mice, Transgenic; Promoter Regions, Genetic; Receptor, Macrophage Colony-Stimulating Factor; Receptors, Nerve Growth Factor; Tacrolimus; Tacrolimus Binding Proteins