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111.
Conditional inactivation of Fgf4 reveals complexity of signalling during limb bud development 总被引:12,自引:0,他引:12
Development of the vertebrate limb bud depends on reciprocal interactions between the zone of polarizing activity (ZPA) and the apical ectodermal ridge (AER). Sonic hedgehog (SHH) and fibroblast growth factors (FGFs) are key signalling molecules produced in the ZPA and AER, respectively. Experiments in chicks suggested that SHH expression in the ZPA is maintained by FGF4 expression in the AER, and vice versa, providing a molecular mechanism for coordinating the activities of these two signalling centres. This SHH/FGF4 feedback loop model is supported by genetic evidence showing that Fgf4 expression is not maintained in Shh-/- mouse limbs. We report here that Shh expression is maintained and limb formation is normal when Fgf4 is inactivated in mouse limbs, thus contradicting the model. We also found that maintenance of Fgf9 and Fgf17 expression is dependent on Shh, whereas Fgf8 expression is not. We discuss a model in which no individual Fgf expressed in the AER (AER-Fgf) is solely necessary to maintain Shh expression, but, instead, the combined activities of two or more AER-Fgfs function in a positive feedback loop with Shh to control limb development. 相似文献
112.
A learning deficit related to age and beta-amyloid plaques in a mouse model of Alzheimer's disease 总被引:21,自引:0,他引:21
Chen G Chen KS Knox J Inglis J Bernard A Martin SJ Justice A McConlogue L Games D Freedman SB Morris RG 《Nature》2000,408(6815):975-979
Mice that overexpress the human mutant amyloid precursor protein (hAPP) show learning deficits, but the apparent lack of a relationship between these deficits and the progressive beta-amyloid plaque formation that the hAPP mice display is puzzling. In the water maze, hAPP mice are impaired before and after amyloid plaque deposition. Here we show, using a new water-maze training protocol, that PDAPP mice also exhibit a separate age-related deficit in learning a series of spatial locations. This impairment correlates with beta-amyloid plaque burden and is shown in both cross-sectional and longitudinal experimental designs. Cued navigation and object-recognition memory are normal. These findings indicate that A beta overexpression and/or A beta plaques are associated with disturbed cognitive function and, importantly, suggest that some but not all forms of learning and memory are suitable behavioural assays of the progressive cognitive deficits associated with Alzheimer's-disease-type pathologies. 相似文献
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114.
某些植物不能将它们的基因保持在体内,但这真的要紧吗?恶梦般的景象可能是这样展开的:农民用经过遗传工程处理使之带有战胜害虫和病害的基因的作物来覆盖他们的农田。这些作物将它们的基因传递给了野生亲缘植物,将它们变成具有超竞争力的杂草,这些杂草将整个农村闹得天翻地覆,消灭掉稀有的和脆弱的物种。环境保护主义者全线反击。面对造成严重损害的诉讼,生物工程公司提出申请破产。科林·梅里特对此感叹不已。在此以前他已经上千次听到过这样的说法,但他当时并不在意。‘“超级杂草”是这样一种带感情色彩的词汇,他说:“它还没有… 相似文献
115.
116.
E A Rogaeva S Premkumar J Grubber L Serneels W K Scott T Kawarai Y Song D L Hill S M Abou-Donia E R Martin J J Vance G Yu A Orlacchio Y Pei M Nishimura A Supala B Roberge A M Saunders A D Roses D Schmechel A Crane-Gatherum S Sorbi A Bruni G W Small P M Conneally J L Haines F Van Leuven P H St George-Hyslop L A Farrer M A Pericak-Vance 《Nature genetics》1999,22(1):19-22
117.
Thirty - nine Utah streams were sampled for cutthroat trout. Of these, 31 contain cutthroat or cutthroat / rainbow hybrid populations. By using starch gel electrophoresis, these populations were segregated into three groups. One group consisted predominately of fish from the Sevier River (of the Bonneville Basin) and Colorado drainages. A second was primarily populations from the Bear River Drainage (Bonneville Basin) as well as some scattered populations along the Wasatch Front (Bonneville Basin). The third consisted of Wasatch Front populations and populations that have hybridized with rainbow trout. Since different subspecies of cutthroat trout are native to the Colorado and Bonneville drainages, one would expect the populations from within the Bonneville Basin to be more similar to one another and less similar to the Colorado River populations. That this did not occur raises questions concerning the evolutionary relationships of the subspecies and the populations. It is clear that at least a northern (Bear River) and southern (Sevier River) form of the Bonneville cutthroat exists. The Wasatch Front may represent an intermediate zone where these two forms intergrade. 相似文献
118.
Hypothalamic tyrosine hydroxylase (TH) activity of castrate rats is modulated by testosterone propionate (TP) in vivo. Kinetic studies revealed that both Vmax and Km were virtually unaltered for substrate tyrosine in the presence of an excess of DMPH4 cofactor. TP replacement to castrate rats increased the Km for added DMPH4 cofactor, while Vmax decreased. These results suggest that TP decreases TH activity of castrate rats by inhibiting the enzyme-reduced pteridine cofactor complex. 相似文献
119.
The reproductive cycle in Belding ground squirrels was studied in the Sierra Nevada Mountains at two locations, one at 2,100 m elevation, the other at 3,000 m. Adults emerged from hibernation completely prepared physiologically for reproduction. Males tended to emerge slightly ahead of females and yearlings tended to emerge later than adults. Yearling females were fertile but produced smaller litters than adults, 4.48 vs. 6.31. Yearling males were infertile. They exhibited a slight seasonal cycle in testicular growth but did not reach sexual maturity. Testicular growth and spermatogenesis were incipient in many adults and in yearlings prior to hibernation. 相似文献
120.
Chia-Ching Lin Yuan-Ju Wu Bernd Heimrich Martin Schwemmle 《Cellular and molecular life sciences : CMLS》2013,70(22):4399-4410
Borna disease virus (BDV) persistently infects neurons of the central nervous system of various hosts, including rats. Since type I IFN-mediated antiviral response efficiently blocks BDV replication in primary rat embryo fibroblasts, it has been speculated that BDV is not effectively sensed by the host innate immune system in the nervous system. To test this assumption, organotypical rat hippocampal slice cultures were infected with BDV for up to 4 weeks. This resulted in the secretion of IFN and the up-regulation of IFN-stimulated genes. Using the rat Mx protein as a specific marker for IFN-induced gene expression, astrocytes and microglial cells were found to be Mx positive, whereas neurons, the major cell type in which BDV is replicating, lacked detectable levels of Mx protein. In uninfected cultures, neurons also remained Mx negative even after treatment with high concentrations of IFN-α. This non-responsiveness correlated with a lack of detectable nuclear translocation of both pSTAT1 and pSTAT2 in these cells. Consistently, neuronal dissemination of BDV was not prevented by treatment with IFN-α. These data suggest that the poor innate immune response in rat neurons renders this cell type highly susceptible to BDV infection even in the presence of exogenous IFN-α. Intriguingly, in contrast to rat neurons, IFN-α treatment of mouse neurons resulted in the up-regulation of Mx proteins and block of BDV replication, indicating species-specific differences in the type I IFN response of neurons between mice and rats. 相似文献