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991.
The Huntington’s disease mutation has been identified as a CAG/polyglutamine repeat expansion in a large gene of unknown
function. In order to develop the transgenic systems necessary to uncover the molecular pathology of this disorder, it is
necessary to be able to manipulate highly expanded CAG repeats in a cloned form. We have identified a patient with an expanded
allele of greater than 170 repeat units and have cloned the mutant allele in the lambda zap vector. The recovery of highly
expanded repeats after clone propagation was more efficient when repeats were maintained as lambda phage clones rather than
as the plasmid counterparts. Manipulation of the repeats as phage clones has enabled us to generate Huntington’s disease transgenic
mice that contain highly expanded (CAG)115–(CAG)150 repeats and that develop a progressive neurological phenotype.
Received: 7 October 1996 / Revised: 5 December 1996 相似文献
992.
M. Hakoda Naoyuki Kamatani Sakura Kurumada Yuko Hirai Kimitaka Sakamoto Hisashi Yamanaka Chihiro Terai Sadao Kashiwazaki 《Human genetics》1997,99(2):164-170
Both germline and somatic mutations are known to affect phenotypes of human cells in vivo. In previous studies, we cloned
mutant peripheral blood T cells from germline heterozygous humans for adenine phosphoribosyltransferase (APRT) (EC 2.4.2.7)
deficiency and found that approximately 1.3 × 10–4 peripheral T cells had undergone in vivo somatic mutations. Loss of heterozygosity (LOH) was the major cause of the mutations
at the APRT locus since approximately 80% of the mutant T cell clones exhibited loss of normal alleles. In the present study,
we identified three heterozygous individuals for APRT deficiency (representing two separate families), in whom none of the
somatic mutant cells exhibited LOH at the APRT locus. The germline mutant APRT alleles of these heterozygotes from two unrelated
families had the same gross DNA abnormalities detectable by Southern blotting. None of the germline mutant APRT alleles so
far reported had such gross DNA abnormalities. The data suggest that the germline mutation unique to these heterozygous individuals
is associated with the abrogation of LOH in somatic cells. The absence of LOH at a different locus has already been reported
in vitro in an established cell line but the present study describes the first such event in vivo in human individuals.
Received: 10 May 1996 相似文献
993.
A. Falconi D. Lorenzo S. Curti F. R. Morales M. Borde 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》1997,181(2):143-151
The present study was designed to examine the synaptic events in neurons of the pacemaker nucleus of Gymnotus carapo during the increase in rate of the electric organ discharge following activation of Mauthner cells. Pacemaker and relay cells
were investigated using intracellular recordings which were performed under two different conditions: (1) with the pacemaker
nucleus spontaneously discharging and (2) after its activity was abolished by anesthesia. Mauthner axon activation induced
an increase in the rate of pacemaker cell discharges. This response was accompanied by an increase in the slope of the pacemaker
potential (up to 110%) and a depolarization of these cells. The discharges of relay cells followed one to one those of pacemaker
cells. In contrast to that observed in pacemaker cells, only brief depolarizing antidromic effects could be evoked in relay
cells after Mauthner axon activation. In quiescent pacemaker cells, Mauthner cell activation induced a prolonged (up to 500 ms)
depolarizing potential with an average amplitude of 1.92 ± 0.82 mV; its latency was 4.43 ± 1.14 ms. Our data indicate that,
within the pacemaker nucleus, the population of pacemaker cells is the only target for Mauthner cell-evoked, short-latency
excitatory synaptic actions.
Accepted: 1 March 1997 相似文献
994.
995.
Differential effects of the pharmacological manipulation of serotonin systems on cocaine and amphetamine self-administration in rats 总被引:3,自引:0,他引:3
L J Porrino M C Ritz N L Goodman L G Sharpe M J Kuhar S R Goldberg 《Life sciences》1989,45(17):1529-1535
The effects of the administration of serotonergic drugs on infusion rates of rats self-administering cocaine and amphetamine on an FR-10 schedule of reinforcement in daily 4 hour sessions were compared. Pretreatment with fluoxetine (2.5, 5, and 10 mg/kg), an inhibitor of serotonin reuptake, significantly decreased rates of responding maintained by amphetamine, but had no effect on responding maintained by cocaine at any of the doses tested. Pretreatment with cinanserin (3, 10, and 17.5 mg/kg), a serotonergic receptor antagonist, decreased rates of amphetamine self-administration at the highest dose tested, and also had no effect on cocaine self-administration. These data suggest a differential sensitivity of cocaine and amphetamine self-administration to pharmacological manipulation of central serotonin systems. They are consistent with biochemical data which demonstrates a negative correlation between the reinforcing potency of amphetamine-like drugs, but not cocaine-like drugs and their potency at serotonin binding sites. 相似文献
996.
A human gene similar to Drosophila melanogaster peanut maps to the DiGeorge syndrome region of 22q11
Judith M. McKie Helen F. Sutherland Emma Harvey Ung-Jin Kim P. J. Scambler 《Human genetics》1997,101(1):6-12
A Drosophila-related expressed sequence tag (DRES) with sequence similarity to the peanut gene has previously been localized to human chromosome 22q11. We have isolated the cDNA corresponding to this DRES and show that it is a novel member of the family of septin genes, which encode proteins with GTPase activity thought to interact during cytokinesis. The predicted protein has P-loop nucleotide binding and GTPase motifs. The gene, which we call PNUTL1, maps to the region of 22q11.2 frequently deleted in DiGeorge and velo-cardio-facial syndromes and is particularly highly expressed in the brain. The mouse homologue, Pnutl1, maps to MMU16 adding to the growing number of genes from the DiGeorge syndrome region that map to this chromosome. 相似文献
997.
Ralf Heinrich N. Elsner 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》1997,180(3):257-269
Stridulation in many gomphocerine grasshoppers is characterized by specific phase shifts between the two hindlegs as well
as different movement patterns produced by the left and the right leg. The underlying neuronal excitation patterns are generated
by networks on either side of the metathoracic ganglion. The role of the intraganglionic commissures in right-left coordination
and the production of differing movement patterns was investigated by transecting the metathoracic ganglion mediosagittally
in Omocestus viridulus, Chorthippus biguttulus and Chorthippus mollis. In all three species, after this operation both hindlegs produced the same pattern and no longer different movements. The effects of transection on coordination differed: rapid movement rhythms, like
those typical of Ch. biguttulus and the vibratory parts of the song of Ch. mollis, on the two sides drifted with respect to one another. In contrast, the slow rhythms characteristic of O. viridulus and the song subunits of Ch. mollis were completely synchronized. It is inferred that in intact animals the pathways for coordination of the rapid stridulatory
rhythms are exclusively intraganglionic, whereas the phase relations of the slow rhythms are additionally influenced by way
of anterior right-left connections, perhaps within the suboesophageal ganglion.
Accepted: 15 October 1996 相似文献
998.
999.
1000.
Chun Y. Gao Peggy S. Zelenka 《BioEssays : news and reviews in molecular, cellular and developmental biology》1997,19(4):307-315
Cyclin-dependent kinases and their regulatory subunits, the cyclins, are known to regulate progression through the cell cycle. Yet these same proteins are often expressed in non-cycling, differentiated cells. This review surveys the available information about cyclins and cyclin-dependent kinases in differentiated cells and explores the possibility that these proteins may have important functions that are independent of cell cycle regulation. 相似文献