Browsing by Subject "Transgenic mice"

Now showing 1 - 3 of 3
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    Cerebrovascular amyloidosis: Experimental analysis in vitro and in vivo
    (Murcia : F. Hernández, 1999) Walker, L.C.; Durham, R.A.
    With advancing age, the likelihood of Bamyloid deposition in the cerebral vasculature increases, particularly in individuals with Alzheimer's disease. The B-amyloid typically accumulates in the basal lamina of the arteriolar tunica media, and frequently extends into the adjacent neuropil. Cerebrovascular B-amyloid increases the risk of hemorrhagic stroke, and may also play a role in the pathogenesis of AD. Genetic variations have been identified that are causative or risk factors for cerebrovascular B-amyloid, including particular mutations in the genes for 0-amyloid precursor protein, presenilins 1 and 2, and possibly cystatin C, as well as polymorphisms in apolipoprotein E. Cerebrovascular amyloidosis is now being studied in a variety of in vitro and in vivo models, including cultured vascular smooth muscle cells, transgenic mice, and aged animals such as nonhuman primates. Methods for delivering agents selectively to vascular amyloid in living subjects are now being developed, and these techniques are paving the way to the development of diagnostic tools and therapies for cerebrovascular amyloidosis.
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    Cytochemical study of the involvement of cell organelles in formation and accumulation of fibrillar amyloid in the pancreas of NORß transgenic mice
    (F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2001) Dobrogowska, D. H.; Vorbrodt, A. W.; Wegiel, J.; Wang, K. C.; Shoji, M.; Mondadori, C.; Polatis, G.; Giovanni, A.; Wisniewski, H. M.
    Ph osphatase ultrastructural cytoc hemistry was used to evalu ate the participation of cytopl asmic orga nell es in the accumulation of fibrillar amyloid /3 (A13) in exocrine acinar cells and in macrophages of the pancreas of transgenic mice overexpressing a carboxyterminal fragment of A/3 protein prec urso r (A/3PP). Nu cleosid e diph os phata se (N DPase) and glucose-6- ph os ph atase (G6Pase) we re used as cy toc hemi cal markers of the endopl asmi c reti culum (ER), thi amine pyroph osphatase (TPPase) as a ma rke r of th e Golgi apparatu s (GA), and acid phosph atase (AcPase) as a marker of Iysosomes. Monoclonal antibody 4G8 raised aga inst the 17-24 aa sequence of human A/3 protein was used for immunogold loca li za tion of fibrill ar A/3. The results of this study indicate that the fo rmation of A13 in acinar cells occurs directl y in the vacuolar areas of the rough ER (RER) without evident participati on of the elements of the GA, whereas an intimate structural relation with primary Iysosomes suggests their role in modification or digestion of the deposited amyloid. In macrophagcs, fibrillar amyloid was prese nt in numerous cytoplasmic vacuoles located frequ entl y in close proximit y to fl attened saccul es of the ER. This structural pattern revea led simil arity to that observed prev iously in mi croglial cells producing fibrill ar PrP amyloid in scrapi e-infected mice and A/3 in brains of human eld erl y pati ents and in Alzheimer's type brain pathology.
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    Immunopathology of autoimmune gastritis: Lessons from mouse models
    (F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2000) Alderuccio, F.; Toh, B. H.
    Autoimmune gastritis in humans is a chronic inflammatory disease of the stomach accompanied by specific destruction of gastric parietal and zymogenic cells resulting in pernicious anemia. Human gastritis can be accurately reproduced in mice and is characterised by autoantibodies to the a- and B-subunits of the gastric H/K ATPase (the enzyme responsible for gastric acid secretion) and cellular destruction of parietal and zymogenic cells within the gastric gland. Studies with these mouse models have given us our current concepts of the immunopathogenesis of the gastritis. Mouse models have shown that a T cell response is generated to the a- and B-subunits of the H/K ATPase and that an immune response to the B-subunit seems to be required for disease initiation. Using these models, we have defined key events associated with a damaging autoimmune response to the gastric H/K ATPase. The mechanisms associated with the cellular destruction associated with autoimmune gastritis are not know, but may involve signaling through death inducing pathways such as the Fas/FasL and TNF/TNFR pathways. This knowledge should permit us to develop strategies to prevent and treat the gastritis.