Disease relevance of Animals, Genetically Modified

• Ectopic expression of Hox-1.1 leads to death of the transgenic animals shortly after birth and is associated with multiple craniofacial anomalies, such as cleft palate, open eyes at birth, and nonfused pinnae [1].
• CONTEXT: Transgenic animal experiments suggest that increased expression of transforming growth factor beta1 (TGF-beta1) is protective against early tumor development, particularly in breast cancer [2].
• In contrast to wild-type mice, the transgenic animals developed significantly reduced ventricular hypertrophy in response to pressure overload and also did not exhibit induction of the cardiac "fetal" gene program [3].
• The transgenic animals develop hyperfunctioning thyroid adenomas with increased intracellular cAMP levels and high uptake of [125I]iodine and produced elevated levels of circulating triiodothyronine and thyroxine [4].
• By using combinations of knockout and transgenic animals, we show that activation of SXR/PXR is necessary and sufficient to both induce CYP3A enzymes and confer resistance to toxicity by LCA, as well as other xenotoxicants such as tribromoethanol and zoxazolamine [5].

Psychiatry related information on Animals, Genetically Modified

• Tauroursodeoxycholic acid, a bile acid, is neuroprotective in a transgenic animal model of Huntington's disease [6].
• Immunizing transgenic PDAPP mice, which overexpress mutant APP and develop beta-amyloid deposition resembling plaques in Alzheimer's disease (AD), results in a decrease of amyloid burden when compared with non-treated transgenic animals [7].
• Compared to control mice, the transgenic animals showed increased amphetamine-induced locomotor activity and increased concentrations of striatal dopamine and its metabolites dihydroxyphenylacetic acid and homovanillic acid [8].
• NGF and BDNF levels on maze learning are different in wild-type and transgenic animals, indicating that biological markers of AD may be altered on challenge even though equilibrium levels are alike [9].
• The identification of mutations in the Tau gene in frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) has made it possible to express human tau protein with pathogenic mutations in transgenic animals [10].

High impact information on Animals, Genetically Modified

• When the mafG null mutants were bred to small Maf-overexpressing transgenic animals, both loss- and gain-of-function phenotypes were reversed [11].
• The 'allelogenic' mouse line we produced carries a hypomorphic allele of Fgf8, which can be converted to a null allele by mating to cre transgenic animals [12].
• Transgenic animals that express ODR-10 in AWB rather than AWA avoid diacetyl, while maintaining qualitatively normal responses to other attractive and repulsive odorants [13].
• We have used transgenic animals misexpressing different rhodopsins in the major class of photoreceptor cells to demonstrate that ninaA is required for normal function by two homologous rhodopsins, but not by a less conserved member of the Drosophila rhodopsin gene family [14].
• Transgenic animals develop hyperkeratosis of the skin and forestomach--the two sites known to express high levels of the keratin 10 polypeptide in vivo [15].

Chemical compound and disease context of Animals, Genetically Modified

• Thus, this is the first transgenic animal model of chronic hyperglycemia with alterations in glucose homeostasis that are produced without a targeted alteration of pancreatic function [16].
• Albuminuria was reduced in those transgenic animals in which sCrry expression was maximally stimulated (urinary albumin/creatinine = 12.4 +/- 4.3 and 36.9 +/- 7.7 in transgene-positive and transgene-negative animals, respectively; p < 0.001) [17].
• Overproduction of Apo CIII causes elevated plasma triglyceride levels in transgenic animals and is associated with hypertriglyceridemia in humans [18].
• Creatine increase survival and delays motor symptoms in a transgenic animal model of Huntington's disease [19].
• To extend this subject to mice for eventual analysis with genetically modified animals, we looked for effects of thyroid hormone treatment on lordosis behavior of ovariectomized estrogen-treated female mice [20].

Biological context of Animals, Genetically Modified

• Using lacZ as a reporter gene for accurate splicing of variable Sh3' domains, we observe differences in beta-galactosidase expression patterns in transgenic animals that indicate both temporal and spatial regulation of 3' splice choice [21].
• By crossing the TIMP-1 transgenic animals with mice expressing an autoactivating stromelysin-1 transgene targeted to mammary epithelial cells, we obtained a range of mice with genetically engineered proteolytic levels [22].
• In the case of the prolactin gene, high levels of expression in transgenic animals required two cis-active regions; a distal enhancer (-1.8 to -1.5 kb) and a proximal region (-422 to +33 bp) [23].
• More over, RBF2 and dE2F2 act synergistically to antagonize dE2F1-mediated activation, and they co-operate to block S phase progression in transgenic animals [24].
• Studies both in cell culture and in transgenic animals suggest that mutant RARs interfere with normal retinoid-mediated transactivation and granulocytic differentiation [25].

Anatomical context of Animals, Genetically Modified

• We find that BDC2.5 T cell receptor transgenic animals contain a small subset of FoxP3 positive CD4+CD25+CD69- cells in the pancreas, actively turning over, expressing the clonotypic receptor, and containing functional regulatory activity [26].
• Regulation of expression of human MHC class I genes in extra-embryonic trophoblast in transgenic animals is thus under conserved selective pressure that is retained across a species barrier [27].
• IL-13 selectively stimulated TGF-beta(1) production in transgenic animals and macrophages were the major site of TGF-beta(1) production and deposition in these tissues [28].
• In normal mice, the IL-9 receptor was found to be expressed by CD5(+) as well as CD5(-) B-1 cells, and repeated injections of IL-9 resulted in accumulation of B-1 cells in the peritoneal cavity, as observed in transgenic animals [29].
• Transection of the sciatic nerve in transgenic animals resulted in induction of human NGF receptors, indicating that the inserted gene can be appropriately regulated [30].

Associations of Animals, Genetically Modified with chemical compounds

• Although the mechanism used by TCR beta chains to deliver such signals is unknown, studies in transgenic animals have suggested that the lymphocyte-specific protein tyrosine kinase p56lck may impinge on a similar signalling pathway [31].
• Thus, we have produced the first transgenic animals that overexpress a soluble C3 convertase inhibitor. rsCrry expression markedly ameliorates an Ab-induced disease model in vivo [32].
• In addition, transgenic animals displayed airway hyperresponsiveness to methacholine in the absence of aerosolized antigen challenge [33].
• The decline in specific activity of the 2-deoxy-3H-glucose, a measure of glucose appearance in the circulation, was more marked in transgenic animals (P < 0.05) [34].
• In summary, these studies suggest that CETP has a much more profound effect on HDL cholesterol levels in transgenic animals expressing human apo A-I [35].

Gene context of Animals, Genetically Modified

• In the present study, transgenic animals were immunized with Abeta42, either before the onset of AD-type neuropathologies (at 6 weeks of age) or at an older age (11 months), when amyloid-beta deposition and several of the subsequent neuropathological changes were well established [36].
• We identify two independent destruction signals in Gli1, D(N) and D(C), and show that removal of these signals stabilizes Gli1 protein and rapidly accelerates tumor formation in transgenic animals [37].
• In TAP1-deficient, HLA-B27 transgenic animals, HLA-B27 molecules fail to assemble correctly, and do not undergo carbohydrate modifications associated with the Golgi apparatus, such as conversion to Endoglycosidase H resistance, and acquisition of sialic acids [38].
• The recent observations of tumor formation in Apobec-1 transgenic animals, together with the fact that Apobec-1 is expressed in numerous tissues lacking apo-B, raises the issue of whether this enzyme is essential for a variety of posttranscriptional editing events [39].
• To accomplish this we generated transgenic animals that carry a Prm1 transgene lacking its normal 3' untranslated region [40].

Analytical, diagnostic and therapeutic context of Animals, Genetically Modified

• The specificity of the Tet repressor-operator-effector interaction and the pharmacological characteristics of Tc's make this regulatory system well suited for the control of gene activities in vivo, such as in transgenic animals and possibly in gene therapy [41].
• Increased levels of B lymphocyte stimulator (BLyS) are associated with systemic autoimmunity in animal models of spontaneous autoimmune disease, and transgenic animals expressing BLyS develop typical autoimmune disease [42].
• Although the blood levels of soluble TNF and IFN-gamma were increased in transgenic animals after challenge with Con A, no damage of hepatocytes could be detected, as assessed by the lack of increase in plasma transaminase activities and the absence of TUNEL staining in the liver [43].
• Furthermore, incorporation of membrane-bound complement regulators (decay-accelerating factor (CD55), membrane co-factor protein (CD46), CD59) in transgenic animals has provided a major step forward in protecting xenografts from hyperacute rejection [44].
• The transgenic animals expressed the human gene-derived mRNA, as revealed by reverse-transcriptase/PCR analysis, in all tissues studied and displayed tissue spermidine synthase activity that was 2-6 times that in their syngenic littermates [45].

References