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In a search for genes that regulate circadian rhythms in mammals, the progeny of mice treated with N-ethyl-N-nitrosourea (ENU) were screened for circadian clock mutations. A semidominant mutation, Clock, that lengthens circadian period and abolishes persistence of rhythmicity was identified. Clock segregated as a single gene that mapped to the midportion of(More)
As a complementary approach to positional cloning, we used in vivo complementation with bacterial artificial chromosome (BAC) clones expressed in transgenic mice to identify the circadian Clock gene. A 140 kb BAC transgene completely rescued both the long period and the loss-of-rhythm phenotypes in Clock mutant mice. Analysis with overlapping BAC transgenes(More)
We have studied the organization of receptive fields of ganglion cells in the isolated mouse retina and have shown that the organization is similar to that of the cat. Based upon responses to circular and annular stimuli, most ganglion cells (90%; N = 83) had receptive fields with concentric center-surround organization, either ON or OFF center. The plot of(More)
1. The metallochromic indicator dye, arsenazo III, was injected intracellularly into Limulus ventral photoreceptor cells to concentrations greater than 1 mM.2. The absorption spectrum (450-750 nm) of the dye in single dark-adapted cells was measured by a scanning microspectrophotometer. When a cell was light-adapted, the absorption of the dye changed; the(More)
The influenza virus M2 protein was expressed in Xenopus laevis oocytes and shown to have an associated ion channel activity selective for monovalent ions. The anti-influenza virus drug amantadine hydrochloride significantly attenuated the inward current induced by hyperpolarization of oocyte membranes. Mutations in the M2 membrane-spanning domain that(More)
Intracellular recordings were made from axon bearing horizontal cells in isolated retinas (with retinal pigment epithelium removed) of normal and pearl mutant mice superfused with mammalian Ringer's solution. Cells were injected with Lucifer yellow and identified by their morphology and their response wave-forms. On impalement, we measured a dark, resting(More)
Retinal projections to the pretectal and terminal accessory optic nuclei were studied in normal wild-type mice and mutant mice with abnormal optokinetic nystagmus (OKN, Mangini, Vanable, Williams, and Pinto: J. Comp. Neurol. 241:191-209, '85). The mutants used were pearl, which exhibits an inverted OKN in response to stimulation of only the temporal retina,(More)
The M2 ion channel proteins of influenza A and B viruses are essential to viral replication. The two ion channels share a common motif, HXXXW, that is responsible for proton selectivity and activation. The ion channel for the influenza A virus, but not influenza B virus, is inhibited by the antiviral drug amantadine and amantadine-resistant escape mutants(More)
1. Isolated bipolar cells were obtained by enzymic (papain) dissociation of the adult mouse retina. The membrane voltage was clamped and the membrane currents were measured by the whole-cell version of the patch-clamp technique. Isolated bipolar cells and horizontal cells of the goldfish retina were also studied for comparison. 2. Hyperpolarization from the(More)
Significant developments have occurred in our understanding of the mammalian genome thanks to informatics, expression profiling and sequencing of the human and rodent genomes. However, although these facets of genomic analysis are being addressed, analysis of in vivo gene function remains a formidable task. Evaluation of the phenotype of mutants provides(More)