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Homozygous Mice (homozygous + mouse)
Selected AbstractsConsequences for enamel development and mineralization resulting from loss of function of ameloblastin or enamelinEUROPEAN JOURNAL OF ORAL SCIENCES, Issue 5 2009Charles E. Smith Although the nonamelogenin proteins, ameloblastin and enamelin, are both low-abundance and rapidly degrading components of forming enamel, they seem to serve essential developmental functions, as suggested by findings that an enamel layer fails to appear on teeth of mice genetically engineered to produce either a truncated form of ameloblastin (exons 5 and 6 deleted) or no enamelin at all (null). The purpose of this study was to characterize, by direct micro weighing, changes in enamel mineralization occurring on maxillary and mandibular incisors of mice bred for these alterations in nonamelogenin function (Ambn+/+, +/,5,6, ,5,6/,5,6, Enam+/+, +/, ,,/,). The results indicated similar changes to enamel-mineralization patterns within the altered genotypes, including significant decreases by as much as 50% in the mineral content of maturing enamel from heterozygous mice and the formation of a thin, crusty, and disorganized mineralized layer, rather than true enamel, on the labial (occlusal) surfaces of incisors and molars along with ectopic calcifications within enamel organ cells in Ambn,5,6/,5,6 and Enam,/, homozygous mice. These findings confirm that both ameloblastin and enamelin are required by ameloblasts to create an enamel layer by appositional growth as well as to assist in achieving its unique high level of mineralization. [source] Tamoxifen modulates apoptosis in multiple modes of action in CreER miceGENESIS: THE JOURNAL OF GENETICS AND DEVELOPMENT, Issue 12 2008Hirohide Takebayashi Abstract Tamoxifen-inducible Cre (CreER) has become a powerful tool for in vivo manipulation of the genome. Here, we investigated opposing effects of tamoxifen on apoptosis during embryogenesis using Olig2,CreER knock-in mice, namely, tamoxifen-induced apoptosis through CreER-mediated toxicity and cytoprotective activity of tamoxifen independent of CreER. First, we examined tamoxifen-induced apoptosis; in the homozygous mice, we observed region-specific apoptosis in the ventral neural tube, with no obvious increase in the heterozygotes. Next, we detected a cytoprotective effect on apoptosis in the homozygous dorsal root ganglia (DRG). This apoptosis is a secondary phenotype of Olig2 -null mice, as Olig2/CreER is not expressed in the DRG. The cytoprotective effect is DRG-specific, because tamoxifen did not rescue apoptosis in the interdigital mesenchyme. These data indicate that tamoxifen has multiple effects on apoptosis during development and caution that careful examination is necessary when interpreting results obtained from tamoxifen-induced recombination: in Olig2-CreER mice, heterozygotes are usable for lineage-tracing experiment without obvious toxicity, while homozygotes show efficient recombination, despite enhanced apoptosis. genesis 46:775,781, 2008. © 2008 Wiley-Liss, Inc. [source] Tissue histopathology, clinical chemistry and behaviour of adult comt -gene-disrupted miceJOURNAL OF APPLIED TOXICOLOGY, Issue 4 2003Kristiina Haasio Abstract Catechol- O -methyltransferase (COMT) enzyme is a widely distributed enzyme that catalyses O -methylation of catecholamines and other compounds having a catechol structure. Because there has been some concern about the consequences of a low COMT activity in the development of oestrogen-dependent cancers and because one of the COMT inhibitors, tolcapone, has caused serious liver injuries in Parkinsonian patients, the histopathology and clinical chemistry of Comt -gene-disrupted mice were studied at the age of 12 months. Owing to the high COMT activities in liver and kidney and the role of COMT in the metabolism of catechol oestrogens, special emphasis was given to the histology of the liver, kidney and oestrogen-dependent organs such as mammary glands and uterus. The mice of both heterozygous and homozygous genotypes appear to be physically healthy and fertile. Diurnal motility rhythm and behaviour in measuring anxiety and depression were equal in all genotypes. At the age of 12 months, the body weight of homozygous mice was 7,9% lower than that of the other groups. This was re,ected in histology as a diminished incidence of vacuolation of liver cells (fatty change). Macroscopic pathology and histopathology revealed no abnormal ,ndings in any COMT genotype. The values of some clinical chemistry parameters, such as alkaline phosphatase, alanine aminotransferase, urea, glucose, calcium and proteins, were at a higher level in homozygous animals compared with the wild-type mice. However, all the values remained within the normal physiological range, and the differences in enzyme levels between genotypes were not re,ected as histopathological ,ndings in the relevant organs. No changes in haematological parameters or plasma catecholamine concentrations were noted but plasma 3,4-dihydroxyphenylethylene glycol levels were high in COMT null mice. The results suggest that the full or 50% lack of Comt gene as such is not associated with any toxic consequences. Copyright © 2003 John Wiley & Sons, Ltd. [source] Cell cycle-driven neuronal apoptosis specifically linked to amyloid peptide A,1,42 exposure is not exacerbated in a mouse model of presenilin-1 familial Alzheimer's diseaseJOURNAL OF NEUROCHEMISTRY, Issue 2 2008Bilal Malik Abstract We have shown previously that ,-catenin and cyclin D1 are up-regulated in cortical neurons from homozygous mice carrying the familial Alzheimer's disease (FAD) presenilin-1 M146V mutation in a knock-in model (PS1 KIM146V mice), leading to cell cycle-associated apoptosis. Here, we have aimed to determine (i) whether this phenotype is present in heterozygous PS1 KIM146V mice, which reflects more accurately the PS1 FAD condition in humans and (ii) whether A,1,42, which is invariably present in the PS1 FAD brain and is thought to affect neuronal cell cycle kinetics, may contribute to the abnormal cell cycle/cell death phenotype seen in PS1 KIM146V mice. We demonstrate that cell cycle-linked apoptosis occurs in heterozygous PS1 KIM146V post-mitotic neurons. In addition, there is a significant A,-associated increase in cell cycle and cell death that is not further modified by the PS1 KIM146V mutation. Our results are consistent with a cell cycle-associated neurodegeneration model in the PS1 FAD brain in which the loss of PS1-dependent ,-catenin regulatory function is sufficient to commit susceptible neurons to an abortive cell cycle, and may act synergistically with the A, cytotoxic challenge present in the PS1 FAD brain to expand the neuronal population susceptible to cell cycle-driven apoptosis. [source] Flanking genomic region of Tyr::Cre mice, rapid genotyping for homozygous micePIGMENT CELL & MELANOMA RESEARCH, Issue 4 2007Sophie Colombo No abstract is available for this article. [source] | ||||||||||