Search PubMed⌕ Search

Biomedical subjects

J W Gordon

Publications and source records attributed to J W Gordon.

106 records · Page 6Linked to original sources
PubMed1981

Integration and stable germ line transmission of genes injected into mouse pronuclei.

Genetic material has been successfully transferred into the genomes of newborn mice by injection of that material into pronuclei of fertilized eggs. Initial results indicated two patterns of processing the injected DNA: one in which the material was not integrated into the host genome, and another in which the injected genes became associated with high molecular weight DNA. These patterns are maintained through further development to adulthood. The evidence presented indicates the covalent association of injected DNA with host sequences, and transmission of such linked sequences in a Mendelian distribution to two succeeding generations of progeny.

Animals↗
PubMed1981

Mammalian gonadal determination and gametogenesis.

Although a relationship between the X and Y chromosomes and mammalian sexual development has long been recognized, a detailed understanding of this relation is still lacking. Recent advances in somatic cell genetics and recombinant DNA technology should provide the tools for solving this fundamental problem in developmental genetics.

Animals↗
PubMed1980

Genetic transformation of mouse embryos by microinjection of purified DNA.

A recombinant plasmid composed of segments of herpes simplex virus and simian virus 40 viral DNA inserted into the bacterial plasmid pBR322 was microinjected into pronuclei of fertilized mouse oocytes. The embryos were implanted in the oviducts of pseudopregnant females and allowed to develop to term. DNA from newborn mice was evaluated by the Southern blotting technique for the presence of DNA homologous to the injected plasmid. Two of 78 mice in one series of injections showed clear homology, though the injected sequences had been rearranged. Band intensities from the two positive mice were consistent with the presence of donor DNA in most or all of the cells of the newborns. These results demonstrate that genes can be introduced into the mouse genome by direct insertion into the nuclei of early embryos. This technique affords the opportunity to study problems of gene regulation and cell differentiation in a mammalian system by application of recombinant DNA technology.

Animals↗
PubMed1979

Ontogenesis of spontaneous activity and habituation of activity in the rat pup.

Individual components of activity and habituation of activity were determined throughout the 1st month of life in the rat pup. Total activity increased from 25% at 8 days of age to 68% at 22 days before declining to 49% at 26 days. Total slight activity (predominantly sniffing) increased to a maximum of 33% at 15 days whereas total very active behavior (predominantly ambulation) reached its maximum of 38% at 22 days. Habituation of activity expressed as the mean slope of decrement of activity over the 1st 30 min of the observation period was observed in rats as young as 8 days of age. By 12 days, habituation of total activity had increased significantly reflecting a 3-fold increase ihabituation of slight activity, an effect observed at 15 days as well. However, by 19 days the slope of activity decrement had declined to half of its 15-day value, indicating an impairment of habituation and reflecting the attenuation of very active behavior, predominantly ambulation. This decline in habituation continued through 22 days but by 26 days habituation of activity had increased again reaching a maximum for the 1st month of postnatal life. Our results suggest that the phenomenon of behavioral arousal observed in the developing rat pup 19 days of age reflects an inability of the organism to modulate his activity as effectively as the 15-day- or 26-day-old animal.

Animals↗
PubMed1978

Methylphenidate in 6-hydroxydopamine-treated developing rat pups. Effects on activity and maze performance.

In order to better devine the relationship between brain catecholaminergic mechanisms and the clinical syndrome of minimal brain dysfunction, we have developed an experimental model that has many of the features of the disorder seen in children. This model is effected by the preferential depletion of brain dopamine in 5-day-old rat pups following the intracisternal administration of 6-hydroxydopamine, and in the present investigation, we have examined the effects of methylphenidate hydrochloride (0.25 to 2.0 mg/kg) on activity levels and cognitive performance in normal and 6-hydroxydopamine treated animals. Methylphenidate therapy resulted in a significant increase in activity levels of normal rat pups 12 and 19 days of age; in contrast, methylphenidate administered to 6-hydroxydopamine-treated animals did not increase activity at 12 days of age and significantly reduced activity at 19 and 26 days. Methylphenidate had no effect on T-maze performance in normals, but significantly improved performance in 6-hydroxydopamine-treated animals. Our results suggest that the "paradoxical" response to methylphenidate found in 6-hydroxydopamine-treated rat pups may be the result of central denervation supersensitivity.

Age Factors↗
PubMed1978

Ontogeny of brain catecholamine turnover and susceptibility to audiogenic seizures in DBA/2J mice.

We have investigated the relationship between catecholamine turnover and susceptibility to audiogenic seizures (AGS) in the developing DBA/2J mouse. Turnover of dopamine and norepinephrine was determined after administration of alphamethylparatyrosine at 3 weeks of age when nearly all mice (94%) exhibited AGS, at 6 weeks when only 30% were susceptible, and at 12 weeks when none developed seizures. Turnover of brain dopamine increased progressively from 236 ng/g/hr at 3 weeks to 389 ng/g/hr by 12 weeks of age. Norepinephrine turnover increased significantly between 3 and 6 weeks of age, then remained stable thereafter. Turnover times for each catecholamine did not change appreciably with maturation. Our results support the notion that susceptibility to AGS may be mediated in part by brain catecholaminergic mechanisms.

Acoustic Stimulation↗
PubMed1977

The effect of 6-hydroxydopamine on habituation of activity in the developing rat pup.

The role of brain catecholaminergic mechanisms in habituation of activity was investigated in rat pups treated with 6-hydroxydopamine (6-OHDA). Intracisternal administration of this agent in the neonatal period resulted in a permanent and significant depletion of brain dopamine to 35.5% of controls while brain norepinephrine remained unchanged. Activity levels in normal developing rat pups increased rapidly between 15-22 days, then declined at maturity (26 days), while activity in 6-OHDA treated animals during this peak period of behavioral arousal increased to a significantly greater degree than that of their littermate controls. Habituation of activity, defined as the decrement of spontaneous activity, was calculated by regression over the first 30 min of observation. At both 5 and 8 days of age 6-OHDA and control rat pups exhibited low levels of activity whose decrease with time did not differ significantly and this pattern continued through 12 days of age. However, by 15 days of age activity in control animals declined by 19% each 10 min period compared to only a 10% decline found in 6-OHDA animals. At 19 days normal rat pups declined by 10% compared to a significantly reduced decrement of 3% found in treated animals, but these differences were no longer apparent by 22, 26, or 29 days of age. Our results are consistent with the notion that habituation of activity is a complex phenomenon mediated in part by catecholaminergic systems.

Aging↗
PubMedDate not supplied

Use of zona drilling for safe and effective biopsy of murine oocytes and embryos.

With the mouse as a model, we have used zona drilling to devise procedures for safe removal of the first polar body or one or more blastomeres from cleaving embryos. These methods require minimal disruption of the zona pellucida and little or no direct contact between microtools and the materials to be biopsied. Of 175 eggs subjected to the polar body biopsy procedure, 1 was killed, and 165/174 survivors were fertilized (94.8%). For blastomere biopsy, embryos from the 2- to 16-cell stage were incubated in a chelating medium containing 100 mM sucrose for at least 30 min. The zonae were then drilled, and one or more blastomeres were "pushed" out through the hole by pressure exerted against the zona at some distance from the drilling site. In all 85 embryos biopsied, one or more additional intact blastomeres were successfully removed. Moreover, 83/84 biposied embryos that were subsequently cultured developed into blastocysts (98.8%). Although acid Tyrode's solution was used in this study, mechanical methods of zona opening were also effective. The data indicate that oocyte and embryo biopsy assisted by zona drilling is safe and does not appear to affect fertilization or development, and as such, it is applicable to genetic diagnostic procedures.

Animals↗
PubMedDate not supplied

Superoxide dismutase and neurofilament transgenic models of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a devastating neurologic disease characterized by progressive motor dysfunction that leads to paralysis and eventually death. There are numerous hypotheses for the pathogenesis of this disease, but the mechanisms of degeneration were difficult to investigate before the development of animal models. Transgenic mice with alterations in either the superoxide dismutase (SOD-1) or neurofilament genes display motor neuron pathology and deficits in motor function and, therefore, provide animal models for the study of ALS neurodegeneration. Using these animal models, as well as several in vitro models, researchers have made rapid progress during the last several years toward understanding the cause and mechanism of ALS neurodegeneration. These studies have demonstrated that motor neuron degeneration in ALS may be secondary to a number of causes, including neurofilament disruption, mutations in SOD-1, and glutamate excitotoxicity. Although each of these mechanisms can cause motor neuron degeneration by itself, studies of transgenic mice have indicated several points at which these mechanisms may interact, suggesting that they are components of one general mechanism of neurodegeneration.

Amyotrophic Lateral Sclerosis↗