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Biomedical subjects

D P Doolittle

Publications and source records attributed to D P Doolittle.

At least 19 recordsLinked to original sources

Selective breeding for alcohol preference and associated responses.

Selective breeding for high and low alcohol-drinking preference has produced rat lines useful for studying the nature of excessive alcohol-seeking behavior. Compared with the alcohol-nonpreferring line, the preferring animals exhibit heightened responsivity to the low-dose activating effects of ethanol as well as enhanced capacity for developing tolerance to the aversive, behaviorally impairing effects of ethanol. The preferring animals exhibit lower brain serotonin and dopamine neurotransmitter activity as well as differences in other neurotransmitter neuromodulator systems, compared with the alcohol-nonpreferring animals.

Alcohol Drinking↗

Lifetime parental productivity in twenty-seven crosses of mice. I. Birth traits.

Twenty-seven crosses derived from three random-mating, unselected strains of mice (SWO, J, PGH) with 16 matings/pureline or cross were cohabited continuously and monogamously for 365 d to evaluate long-term reproductive performance of the parents. Data from 3,249 litters born were analyzed to study the effects of parity (number of litters) and type of cross (pureline, two-way, backcross, three-way) on the following traits: 1) continuity of reproduction (COR), 2) litter size at birth (LSB), 3) age at first litter (AFL), 4) fraction alive at birth-the ratio of number born alive to LSB (FAB), 5) birth to birth interval (BBI) and 6) reproductive rate-the ratio of number born alive to birth to birth interval (RRT). Reproductive rate was also studied in a cumulative manner rather than on a per parity basis by regressing cumulative number born alive on cumulative birth to birth interval. Parity effects were important (P less than .01) for all traits measured. Differences among cross-types were highly significant for COR, LSB and RRT. Three-way crosses were more productive than backcrosses, and both were superior to two-way and pureline matings. Uniformity was greater among three-way crosses for all traits except COR. Cross-types differed importantly in the pattern of change in performance over parities for COR, LSB, FAB, RRT and cumulative number of live young (P less than .01). Number of parities were most important for variation in longevity of reproduction (COR) and somewhat for litter size (LSB). Mean and cumulative reproductive rates were influenced more by longevity and litter size than by interval between births.

Animals↗

Lifetime parental productivity in twenty-seven crosses of mice. II. Weaning traits reflecting reproduction and lactation.

Twenty-seven crosses of mice derived from three random-mating, unselected strains (SWO, J. PGH) with 16 matings/pureline or cross were cohabited continuously and monogamously for a 365-d reproduction period to evaluate lifetime reproductive performance of the parents. Data from 3,249 litters born (2,792 surviving to weaning) were analyzed to study the effects of parity (number of litters) and type of cross (pureline, two-way, backcross, three-way) on certain traits measured at weaning (21 d). The traits evaluated were 1) weaning to weaning interval (WWI), 2) litter size at weaning (LSW), 3) fraction alive at weaning (FAW)-the ratio of LSW to number born alive, 4) total litter weight at weaning (LWT), 5) pup weight at weaning (PWT), 6) weaning weight per pup observed alive at birth (WPP), 7) parental feed consumption per day (FPD) and 8) parental costs (PCT). Cost per live weanling animal was estimated as the ratio of cumulative parental costs to cumulative number weaned. Cost per unit of weaning weight was defined as the regression of cumulative parental costs on cumulative litter weight. Parity effects were important (P less than .01) for all traits measured. Type of cross effects were noted for LSW, LWT, PWT, WPP, FPD (P less than .01) and PCT (P less than .05). A parity X cross-type interaction was expressed for WWI, LSW, PWT, WPP, FPD (P less than .01) and FAW (P less than .05). Three-way crosses were more productive than backcrosses, two-way crosses and pureline matings for all traits studied. Three-way crosses displayed the smallest cost per animal weaned and smallest cost per unit of weaning weight. The influence of parity on traits measured at weaning was less than for traits measured at birth. Weight per pup born alive (WPP) was found to be a better indicator of reproduction and lactation ability than LWT because WPP accounts for preweaning mortality.

Animals↗

Effects of age at slaughter and feeding regime on slaughter weight and carcass composition in mice.

Mice from three outbred stocks (PGH, J, and SWO) were fed either pelleted feed from overhead hoppers or ground feed from jars, from weaning at 21 days old to slaughter at 42, 49 or 56 days old. Live weights, weights of carcasses before and after extraction of carcass moisture and fat, and feed consumption were recorded. The PGH stock gained more in dry lean tissue and deposited less fat, and had a greater feed efficiency, compared to either of the other stocks. Males gained more than females, in both dry lean tissue and fat; females had a higher proportion of lean tissue and a greater feed efficiency. Increases in live weight between 49 and 56 days of age were mainly increases in fat content, especially in the offal portion of the body. Jar feeding restricted feed intake and reduced live weight gains. The reduction, however, was principally in fat deposition; feed efficiency was also greater for jar fed mice. It was found that the amount of lean tissue could be accurately predicted from carcass weight and carcass moisture measurements. It may be possible to estimate lean tissue accurately without employing the expensive and time consuming process of either extraction.

Adipose Tissue↗

Genetic basis for the polymorphism of rat liver cytosolic aldehyde dehydrogenase.

Liver aldehyde dehydrogenase (ALDH), the enzyme involved in the oxidation of aldehydes such as acetaldehyde derived from ethanol, exists in multiple forms in most mammals. Up to five separable forms have been identified from the cytosolic fraction of Wistar rat liver. We investigated genetic basis of a particular set of three enzyme forms by selective breeding and analysis of electrophoretic patterns of liver ALDH by isoelectric focusing. The forms of liver ALDH investigated were at pI 5.8 or 6.2 or a triple form with enzymes at pI 5.8, 6.0, and 6.2. There are two alleles found at the ALDH locus which encode in homozygotes for one of two electrophoretically separable ALDH forms. A rat heterozygous at the locus forms both ALDH types plus a hybrid. The alleles are expressed codominantly, found at an autosomal locus, and remain constant postpartum. The activities associated with the triplet enzyme form were statistically indistinguishable from a 1:2:1 ratio. This suggests that the enzymes hybridize to form a set of dimers or tetramers of the form A2, AB, B2, or A4, A2B2, B4, respectively.

Aldehyde Dehydrogenase↗

Skeletal muscle cellularity in mice selected for large body size and in controls.

Body composition and skeletal muscle weights, fiber diameters, fiber numbers, and RNA and DNA concentrations were studied in mice selected for large body size (GLW) compared to an unselected control (C) line. At 60 days of age, body weight of GLW mice was 70 to 75% greater than C mice, but % body water, fat or dry fat-free residue did not differ between the lines. In both GLW and C mice, greater muscle weight in males compared to females was due to larger diameter fibers and not to significant differences in fiber number between sexes, although in most cases, males had slightly higher mean fiber number. Fiber diameters were similar in the two lines and the greater muscle weights of GLW mice were due to more fibers than in the muscles of C mice. RNA and DNA concentrations were slightly, but not significantly, higher in GLW skeletal muscles.

Animals↗

Effect of caging variables on body weight and weight gain in mice.

The effects on body weight of mixing litters to attain constant density of mice per cage, as opposed to housing litters in separate cages, was studied. Mixing litters resulted in a decreased weight gain between 21 and 42 da of age and a decreased adult body weight at 63 da of age compared to housing litters in separate cages, whether the separately housed litters were allowed to vary in density or not. Mixed litter housing also increased the variance of the body weight measures among males. Housing litters separately, even if it entails variable density of housing, appears to be the preferred method for studies involving inheritance of body weight.

Animals↗