ISSN:0265-9247    

DOI:10.1002/bies.950190902

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1997

数据来源: WILEY

摘要:

AbstractAlthough the precise function of utrophin at the postsynaptic membrane of the neuromuscular junction still remains unclear, despite recent genetic ‘knockout’ experiments(1,2), a separate study in a transgenic mouse model system for Duchenne muscular dystrophy (DMD) has nonetheless shown that overexpression of utrophin into extrasynaptic regions of muscle fibers can functionally compensate for the lack of dystrophin and alleviate the muscle pathology(3). In this context, the next step is to identify the mechanisms presiding over expression of utrophin at the neuromuscular synapse in attempts to induce its expression throughout DMD muscle fibers. In fact, additional studies have shown that an important DNA element contained with the utrophin promoter may confer synapse‐specific expression to the utrophin gene(4,5). Identification of the events culminating in the transaction of the utrophin gene within synaptic myonuclei should provide important cues for the development of an effective therapeutic strategy fo

ISSN:0265-9247    

DOI:10.1002/bies.950190903

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1997

数据来源: WILEY

摘要:

AbstractMitochondria are essential subcellular organelles containing an extranuclear genome (mtDNA). Mutations in mtDNA have recently been identified as causing a variety of human hereditary diseases. In most of these cases, the tissues of the affected individual contain a mixture of mutant and normal mtDNA, with this ratio determining the severity of symptoms. Stochastic factors alone have generally been believed to determine this ratio. Jenuthet al.(1), however, examining mice that contain a mixture of mtDNA types, show evidence of strong selective forces at work in favoring one mtDNA variant over another in some tissues.

ISSN:0265-9247    

DOI:10.1002/bies.950190904

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1997

数据来源: WILEY

摘要:

AbstractPaxgenes are a family of development control genes that encode nuclear transcription factors. They are characterized by the presence of the paired domain, a conserved amino acid motif with DNA‐binding activity. Originally, paired‐box‐containing genes were detected inDrosophila malenogaster, where they exert multiple functions during embryogenesis. In vertebrates,Paxgenes are also involved in embryogenesis. Mutations in four out of nine characterizedPaxgenes have been associated with either congenital human diseases such as Waardenburg syndrome (PAX3), Aniridia (PAX6), Peter's anomaly (PAX6), renal coloboma syndrome (PAX2), Small eye (Pax6), (Pax21Neu), which all show defects in development. Recently, analysis of spontaneous and transgenic mouse mutants has revealed that vertebratePaxgenes are key regulators during organogenesis of kidney, eye, ear, nose, limb muscles, vertebral column and brain. Like theirDrosophilacounterparts, vertebratePaxgenes are involved in pattern formation during embryogenesis, possibly by determiing the time and place of organ initiation of morphogenesis. For most tissues, however, the nature of the primary development action of Pax transcription factors remains to be elucidated. One predominant theme is signal transduction during tissue interactions, which may lead to a position‐specific regulation of cell prolif

ISSN:0265-9247    

DOI:10.1002/bies.950190905

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1997

数据来源: WILEY

摘要:

AbstractNerve processes elongate, branch and form synaptic contacts in a highly regulated and specific manner. Long‐distance axon elongation is restricted to the main phase of axon formation during development, but can be reinduced upon lesions in the adult (regeneration). It correlates with the expression of defined genes, including proteins involved in signalling (e.g. src, NCAM, integrins), transcription factors (e.g. c‐jun) and structural proteins (e.g. actin and tubulin isoforms). Activation of an axon elongation program may require bcl‐2. The formation and growth of local branches (sprouting) is controlled by mechanisms in the target region. In addition, the expression of growth‐associated proteins such as GAP‐43 and CAP‐23 in neurons lowers the threshold for nerve sprouting and potentiates its vigour. Recent studies suggest that nerve sprouting and long‐distance elongation depend on the expression of different intrinsic components in neurons. One implication of these findings is that the differential expression of genes facilitating local branching may affect structural plasticity in the intact adult n

ISSN:0265-9247    

DOI:10.1002/bies.950190906

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1997

数据来源: WILEY

摘要:

AbstractAdaptive immunity is unique to the vertebrates, and the molecules involved (including immunoglobulins, T cell receptors and the major histocompatibility complex molecules) seem to have diversified very rapidly early in vertebrate history. Reconstruction of gene phylogenies has yielded insights into the evolutionary origin of a number of molecular systems, including the complement system and the major histocompatibility complex (MHC). These analyses have indicated that the C5 component of complement arose by gene duplication prior to the divergence of C3 and C4, which suggests that the alternative complement pathway was the first to evolve. In the case of the MHC, phylogenetic analysis supports the hypothesis that MHC class II molecules evolved before class I molecules. The fact that the MHC‐linked proteasome components that specifically produce peptides for presentation by class I MHC appear to have originated before the separation of jawed and jawless vertebrates suggests that the MHC itself may have been present at this time. Immmune system gene families have evolved by gene duplication, interlocus recombination and (in some cases) positive Darwinian selection favoring diversity at the amino acid leve

ISSN:0265-9247    

DOI:10.1002/bies.950190907

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1997

数据来源: WILEY

摘要:

AbstractIn eukaryotic cells the nucleus and its contents are separated from the cytoplasm by the nuclear envelope. Macromolecules, as well as smaller molecules and ions, can cross the nuclear envelope through the nuclear pore complex. Molecules greater than approx. 60 kDa and containing a nuclear localization signal are actively transported across the nuclear membranes, but there has been little evidence for regulatory mechanisms for smaller molecules and ions. Recently, diffusion across the nuclear envelope has been observed to be regulated by nuclear cisternal Ca2+concentrations. Following depletion of Ca2+from the nuclear store by inositol 1,4,5‐trisphosphate or Ca2+chelators, a fluorescent 10 kDa marker molecule was no longer able to enter the nucleus. Distinct conformational states of the nuclear pore complexes depended on the Ca2+filling state of the nuclear envelope, supporting the assumption that a switch in the conformation of the nuclear pore complex may control the transport of intermediate‐sized molecules across the nuclear envelope. Thus nuclear Ca2+stores may regulate the conformational state of the nuclear pore complex, and thereby passive diffusion of molecules between the cytosol and the nucleoplasm. The physiological significance of this finding is currently unkn

ISSN:0265-9247    

DOI:10.1002/bies.950190908

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1997

数据来源: WILEY

摘要:

AbstractInsulin‐dependent diabetes mellitus (IDDM) is an autoimmune disease whose etiology is complex. Both genetic susceptibility, which is polygenic, and environmental factors, including virus infections, appear to be involved in the development of IDDM. In this review, we have tried to balance the discussion of diabetes by examining both immunological and virological perspectives. Several mouse models, including viral and non‐viral models, have been used to study diabetes. For this review, we include lessons gleaned from the non‐obese diabetic (NOD) mouse and from mouse models of coxsackievirus‐ and encephalomyocarditis‐virus‐induced diabetes. Finally, we present a multi‐stage model in which several viral infections, including the coxsackieviruses, are postulated to play a role in the autoimmune destruction of pancreat

ISSN:0265-9247    

DOI:10.1002/bies.950190909

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1997

数据来源: WILEY

摘要:

AbstractSpermatogenesis is an elaborate process involving both cell division and differentiation, and cell‐cell interactions. Defects in any of these processes can result in infertility, and in some cases these can be genetic in cause. Mapping experiments have defined at least three regions of the human Y chromosome that are required for normal spermatogenesis. Two of these contain the genes encoding the RNA binding proteins RBM and DAZ, suggesting that the control of RNA metabolism is likely to be an important control point for human spermatogenesis. A similar analysis in mice has shown that at least two regions of the mouse Y chromosome are essential for spermatogenesis. Both genetic and reverse genetic approaches have been used to identify mouse autosomal genes required for spermatogenesis. These studies have shown that genes in a number of different pathways are essential for normal spermatogenesis, and also provide putative models of human infertilit

ISSN:0265-9247    

DOI:10.1002/bies.950190910

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1997

数据来源: WILEY

摘要:

AbstractWe now know that the evolution of multidomain proteins has frequently involved genetic duplication events. These, however, are sometimes difficult to trace because of low sequence similarity between duplicated segments. Spectrin, the major component of the membrane skeleton that provides elasticity to the cell, contains tandemly repeated sequences of 106 amino acid residues. The same repeats are also present in α‐actinin, dystrophin and utrophin. Sequence alignments and phylogenetic trees of these domains allow us to interpret the evolutionary relationship between these proteins, concluding that spectrin evolved from α‐actinin by an elongation process that included two duplications of a block of seven repeats. This analysis shows how a modular protein unit can be used in the evolution of large cytoskeletal struc

ISSN:0265-9247    

DOI:10.1002/bies.950190911

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1997

数据来源: WILEY