Thesis (M.S.)--Villanova University, 2006. / Biology Dept.

Thesis (Ph.D.)--Ohio University, June, 2006. / Includes bibliographical references (leaves 101-122)

The differential susceptibilities of warfarin-susceptible LAC-grey and warfarin-resistant HC house mice to the anticoagulant effect of the oral rodenticide 3-(alpha-acetonyl benzyl)-4-hydroxycoumarin (Warfarin) in terms of their blood clotting times, were determined. The hypoprothrombinaemic effect of both the R(+) and S(-) warfarin enantiomers was also investigated, in addition to the standard test for warfarin-resistance in mice, the ability to survive on a diet containing 0.025% warfarin for 21 days. Onto this base of knowledge of the exact hypoprothrombinaemic responses evoked by treatment of both warfarin- susceptible and warfarin-resistant mice with warfarin at various doses, a structured analysis of the biochemical consequence(s) of expression of the major warfarin-resistance gene, War, could be built. Thus, changes in the in vivo pharmacokinetic parameters including half-life (t[1/2]), plasma clearance (Cl[p]), apparent volume of distribution (Vd[app]) and bioavailability (F) were documented for both R(+) and S(-) warfarin in both males and females of the two mouse strains. Similarly, in vitro hepatic microsomal metabolite profiles following pretreatment with warfarin, phenobarbitone, beta-naphthoflavone and clofibrate, excretion of unchanged warfarin enantiomers and warfarin metabolites and finally plasma protein binding parameters were determined in LAC-grey and HC mice. Therefore, it was possible to correlate changes in the pharmacokinetics, metabolism and disposition of warfarin in these mice with their differential anticoagulant sensitivities. Accordingly, the biochemical mechanism(s) of the expression of the major warfarin-resistance gene, War, has (have) been proposed to be due, at least in part, to a combination of a greater plasma clearance of the more potent S(-) warfarin enantiomer in females, a larger hepatic uptake of the same enantiomer in both sexes, and a greater degree of plasma protein binding of both enantiomers of warfarin.

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No description available.

This study was initiated in an attempt toadd the four-striped field mouse (Rhabdomys pumilio) to the small group of mammals that are used to study and develop assisted reproductive technologies. To accomplish this, a complete knowledge of both the male and female gametes was necessary, as well as a repeatable and successful IVF protocol. The gametes of the field mouse, both the falciformspermand the mature oocytes, were shown to be similar in several respects to those of many other rodent species. The induction of both the capacitated state and the acrosome reaction in the sperm were readily achieved. The success of retrieving mature oocytes was very low, with the rare occurrence of polar bodies within ovulated oocytes. The difficulties with oocytes was either related to the lack of a regular oestrous cycle, or to the hormonal regime used to induce superovulation. Although several protocols were used to accomplish superovulation in this species, it was seldom achieved. In in vitro fertilization trials, sperm were found to attach to both the cumulus oophorus and the zona pellucida of the oocytes. However, fertilization was never accomplished. This failure to achieve fertilization was probably related to the immaturity of the oocytes. Without further studies on Rhabdomys pumilio and further attempts at accomplishing in vitro fertilization, it would seem that this species would not easily be introduced as an animalmodelfor assisted reproduction.

No description available.

Six races of Peromyscus, from a variety of habitats, have been studied with respect to factors involved in adaptation to environmental temperature. The central theme of the study was to assess the extent to which metabolic rate is involved in the processes of distribution and speciation in this genus. A unique, electrolytic respirometer for the accurate measurement of oxygen consumption was constructed and reported in the literature. With this apparatus, the metabolic rate characteristics of the six races were measured over the temperature range 0° to 35°C. After acclimation to standardized laboratory conditions, critical temperatures and metabolic responses to temperatures below thermoneutrality were primarily related to body size. They show, therefore, no evidence of racial metabolic rate adaptation or significant insulative differences. Body weight per se is not correlated with the climate of the respective habitats. A single equation which predicts the metabolic rate of these races at any temperature between 0° and 27°C, from a knowledge of body weight and body temperature, is derived. When considered as a single group, the basal oxygen consumption of all races varied with body weight 0.69 and was insignificantly different from the accepted interspeciesapproximation. The basal metabolic rates of each race showed no temperature-adaptive differences, especially when considered in relation to body composition. The body composition in terms of water, fat and protein was determined for all individuals. The importance of considering body composition, especially fatness, in comparative studies of metabolic rate is emphasized. It is concluded that metabolic rate is inadaptive to climate in these races of Peromyscus and consequently has played no important role in their distribution and speciation. It is shown that the major temperature-adaptive feature of these small mammals is the use of a suitable microclimate. Measurements of the ambient temperatures prevailing in the microhabitats of the six races during winter and summer are presented. These data indicate that there is no significant differential selective pressure for temperature adaptation among the six races, and are complementary to the finding that metabolic rate is inadaptive to gross climate in Peromyscus. / Science, Faculty of / Zoology, Department of / Graduate

In order to clarify some of the problems connected with a study of the growth of meat-producing animals an investigation of certain aspects of growth has been undertaken. Because of the difficulty of conducting large scale experiments with the common meat producing animals, the mouse was chosen for the present study. As a pilot to future work with larger animals, average age changes in body composition and metabolic rate of mice from birth to maturity have been determined. In addition, the effect of plane of nutrition on these two variables and on growth rate and feed efficiency have been investigated. The composition of the body varies in a regular manner with increasing body weight especially on a fat-free basis. Changes in the major constituents apparently exhibit differential growth. The protein to water ratio is suggested as a valid index of physiological age in all mammals. Metabolic rate does not bear a constant relationship to body weight, age, surface area, fat-free mass or protein mass in growing animals. It is, however, directly proportional to the fat-free mass divided by the protein to water ratio and to total body-water. The former expression is considered a valid index of physiologically active mass because it is a function of that fraction of the body which is metabolizing and of changes in its composition. It is the amount of metabolizing tissue corrected to a common physiological age. Plane of nutrition has an effect on growth rate, feed efficiency, body composition and metabolic rate. Restricted nutrition slows up the growth process such that the rate of physiological aging decreases. Thus, most of the changes in the growth complex resulting from restricted nutrition may be due to changes in the relative growth rates of the various body tissues. / Land and Food Systems, Faculty of / Graduate