Direct and correlated responses to selection for increased postweaning gain in mice

Summary Mass selection for increased body weight gain from 21 to 42 days of age was practiced for 12 generations in four replicate lines of ICR-albino mice. Response to selection averaged 0.56±0.03 g. per generation. This response represented an increase of 7.0 genetic standard deviation units and 3.4 phenotypic standard deviation units in 12 generations. The realized heritability pooled over the four replicates was 0.24±0.02. Sizable positive correlated responses were found for 42 and 56-day weight and gain from 42 to 56 days. Much smaller positive correlated responses were noted for 12-day litter weight and 12-day individual weight. Neither litter size nor weaning weight were significantly altered by selection for increased postweaning gain. Reproductive efficiency measured as percent fertile matings declined significantly in the selected lines.Supported in part by a grant from the Virginia Agricultural Foundation.Published with the approval of the Director of the Research Division, Virginia Polytechnic Institute and State University.     

Diallel Analysis of Growth Traits in Mice

Two replications of a complete diallel cross experiment were performed among four partially inbred lines of mice. These inbred lines originated from a random-bred ICR strain and were produced by 12 generations of full sibbing (F congruent to 92%). Individual body weight was recorded for each animal at 12, 21, 42 and 56 days of age. Body weight gain traits were examined for intervals 12-21, 21-42 and 42-56 days. Simultaneous least squares analyses of inbred and linecrossed groups were used. Sex differences were highly significant for all traits. Replicate differences were significant but made a small contribution to the total variation. Inbred lines differed greatly. Crosses showed growth trends similar to their contemporary maternal and paternal inbreds. Heterosis was highly significant for all traits except 21-day weight. Inbreds were heavier at 12 days of age, but linecrossed progeny were superior to inbreds for all postweaning weights. General combining ability was highly significant for 12- and 56-day weights and 21-42-day gain. Specific combining ability was highly significant for 21-day weight, 12-21- and 42-56-day gain. Significant maternal effects were found for all individual weights but not for 12-21- and 21-42-day gain. Residual reciprocal effects were significant for all traits. Estimated variances among linecrossed groups contained a large maternal component, a fluctuating additive genetic component and consistent non-additive genetic influence on all growth parameters measured.     

Long-Term Selection Response for 12-Day Litter Weight in Mice

Long-term selection for increased 12-day litter weight in two replicate lines (W₂, W₃) of mice resulted in an apparent selection limit at about 17 generations. Quadratic polynomial and exponential models were fitted to the data in order to estimate the plateaued response and half-life of the selection process. Using the polynomial results, the half-life estimates were 4.5 and 8.6 generations for W₂ and W₃, respectively. The plateaued responses were 5.1 and 5.8 g which, when expressed in phenotypic standard deviation units, became 1.1 and 1.3. The exponential model provides similar estimates. A negative association between 12-day litter weight and fitness was not considered to be an adequate explanation for the plateau since there was no decrease in fertility of the selected lines. Evidence that exhaustion of genetic variability was not the cause of the plateau came from the immediate response to reverse selection. It was proposed that the plateau may be due to a negative genetic correlation between direct and maternal genetic effects, which would be expected to occur after many generations of selection. There were positive correlated responses in both replicates for adult body weight, which was in agreement with the positive genetic correlation between preweaning and postweaning body weight. The expected positive correlated response for number born was realized in only one of the replicates.     

Utilization of milk energy by suckling mink kits

A total of 36 mink dams and their litters of 3, 6 or 9 kits were used for determination of milk intake of the suckling young by means of deuterium dilution technique, and chemical composition of milk and of kit bodies. Measurements were performed during lactation weeks 1-4, each week with 3 dams with each litter size. Milk intake was determined over a 48 h measurement period, and by the end of this milk samples were collected and 2 kits (litters of 6 and 9) or 1 kit per litter (litters of 3) were killed for body chemical composition. Based on the results, different models were applied for calculation of the energetic efficiency of milk. Dam milk yield increased steadily from week 1 until week 3 but only slightly from week 3 to 4. The increase declined with increasing litter size, and for dams suckling 9 kits the increment from week 3 to week 4 was only 2 g. The dry matter content of milk increased significantly as lactation progressed, being reflected in crude protein increasing from 6.9% in lactation week 1 to 8.1% in week 4. Milk fat increased concomitantly from 5.6% to 8.0%. In kit bodies, crude protein content increased from 9.4% in week 1 to about 12% in weeks 3 and 4. Body fat content increased from week 1 (4.1%) to week 3 (8.4%) and then declined in week 4 (7.1%). Animals suckled in litters of 3 kits had the highest milk intake and live weight and kits suckled in litters of 9 had the lowest milk intake, live weight and daily gain. In terms of milk intake per g gain kits in litters of 6 were the most efficient, with 4.1 g milk per g body gain. The metabolizable energy requirement for maintenance (MEm) was estimated to 448 kJ/kg(0.75 and the efficiency of utilization of ME for body gain (kg) to 0.67, the estimates being higher (MEm) or in good agreement with previous findings (kg) in suckling mink kits.     

Heterosis, sex and maternal interactions in crosses among inbred lines of mice.

All possible crosses and reciprocals were made among four inbred lines (F = 92%) developed from 12 generations of full-sib mating. All lines originated from a common outbred base population of ICR-albino mice. Data were obtained from 356 litter containing 2,734 mice to evaluate heterosis, reciprocal effects, sex effects and their interactions as they affect body weight and weight gain. Heterosis was significant for most of the postweaning traits (42- and 56-day weight and gain from 21 to 42 days). Nonadditive gene action may have included overdominance and epistasis since both reciprocal linecrosses were generally heavier than those of the better inbred lines. Although significant differences in reciprocals and inbred lines were not frequent, there were sufficient differences to indicate that lines varied in the fixation of loci during inbreeding. Sex-heterosis interactions were significant for 12 of 30 possible cases. However, eight of the 12 significant interactions occurred in crosses involving only one of the lines. The interactions were of the divergent type and arose from males exhibiting more heterosis than females. Overdominance in genes on the sex chromosomes modified by other loci (epistasis) was proposed as a possible explanation for these results. Some sex-linkage affecting growth was evident from the interaction of sex with reciprocal effects.     

Selection for fertility in mice using different methods of litter size manipulation

Summary A short-term selection experiment for increasing the first-day litter size (LS1) and 28-day litter weight (LW28) was conducted with three populations of mice over 8 generations. Different methods of litter size manipulation were used for the populations — in S the litter size was standardized to 8 (4 , 4 ) on the first day, in LA it was adjusted to the average size of all litters born on the same day and NL had the natural litter size. To eliminate temporary environmental effects, a control population was kept in each case. The selection results per generation were, for LS 1 b=0.30 (S, NL) and 0.20 (LA), and for LW28 b=5.62 g (S), 5.26 g (NL), and 4.32 g (LA). The heritability obtained was between 0.18 and 0.13 for LS 1 and from 0.42 to 0.12 for LW28. The populations differed in the correlated responses for body weight parameters (litter weight gain). The implantation rate increased in populations S and NL (b=0.19, 0.37), but not in population LA. Postnatal mortality went down (b=-0.07) and the dam's milk production rose (b=1.11 g) only in population LA. The estimated partial regression coefficient linking body weight at mating (BWM) for the dam and the daughter's litter size showed an effect on the litter size.     

Utilization of milk energy by suckling mink kits

A total of 36 mink dams and their litters of 3, 6 or 9 kits were used for determination of milk intake of the suckling young by means of deuterium dilution technique, and chemical composition of milk and of kit bodies. Measurements were performed during lactation weeks 1?–?4, each week with 3 dams with each litter size. Milk intake was determined over a 48?h measurement period, and by the end of this milk samples were collected and 2 kits (litters of 6 and 9) or 1 kit per litter (litters of 3) were killed for body chemical composition. Based on the results, different models were applied for calculation of the energetic efficiency of milk. Dam milk yield increased steadily from week 1 until week 3 but only slightly from week 3 to 4. The increase declined with increasing litter size, and for dams suckling 9 kits the increment from week 3 to week 4 was only 2?g. The dry matter content of milk increased significantly as lactation progressed, being reflected in crude protein increasing from 6.9% in lactation week 1 to 8.1% in week 4. Milk fat increased concomitantly from 5.6% to 8.0%. In kit bodies, crude protein content increased from 9.4% in week 1 to about 12% in weeks 3 and 4. Body fat content increased from week 1 (4.1%) to week 3 (8.4%) and then declined in week 4 (7.1%). Animals suckled in litters of 3 kits had the highest milk intake and live weight and kits suckled in litters of 9 had the lowest milk intake, live weight and daily gain. In terms of milk intake per g gain kits in litters of 6 were the most efficient, with 4.1?g milk per g body gain. The metabolizable energy requirement for maintenance (MEm) was estimated to 448 kJ/kg^0.75 and the efficiency of utilization of ME for body gain (k_g) to 0.67, the estimates being higher (MEm) or in good agreement with previous findings (k_g) in suckling mink kits.     

Population Size and Selection Intensity Effects on Long-Term Selection Response in Mice

Long-term response to within full-sib family selection for increased postweaning gain was evaluated in lines having different effective population sizes (N_e) and selection intensities (i). Line designations were I4(4), I8(2), I16(2), M4(4), M8(2) and M16(2), where I and M indicate selection of the top 50% and 25%, respectively; 4, 8 and 16 represent the number of parental pairs per replicate and number of replicates is given in parentheses. Realized within full-sib family heritabilities (h_R²) in the first phase of selection (0-14 generations) were larger in 16-pair lines than in 4- and 8-pair lines. In the second phase of selection (>14 generations), h_R² declined significantly (P<.01) in all lines, and only the I16 and M16 lines had h_R² values significantly (P<.01) greater than zero. Realized genetic correlations involving number born, 12-day litter weight, weaning weight and six-week weight tended to decline in the second phase of selection. The I16, M16 and control (C16) replicates were crossed in all combinations at generation 14. Crosses were then selected within litters for high postweaning gain. The h_R² values in the crossbred lines were all larger than those in the second selection phase for M16-1, M16-2 and I16-1, but not for I16-2. Within each N_e level, total response was significantly (P<.01) less for I lines compared with M lines. Total response increased as N_e increased, within each level of i. Relatively small differences in realized i values among N_e lines could not account for this result. The difference in total response among the N_e lines at a given selection intensity may be due to inbreeding depression and a combination of interactions involving "drift" and selection. By crossing replicates of the M lines with the C16 control, the effects of inbreeding depression were removed. Inbreeding depression and genetic drift, as defined herein, were equally important in accounting for differences among N_e lines in total response.     

Cranial postnatal growth of the rat relative to environmental variance

Neurocranial growth during the first 40 days of postnatal development was biometrically investigated relative to the specific parameters of calvarium length and width; basioccipital length and width; basisphenoid length; biparietal width; frontal bone length and cranial vault length. Specimens were obtained from rat litters subject to moderate nutritional suppression by raising the litter numbers above the norm via the cross-fostering technique and causing the overtaxing of the lactational capacity. Alterations in growth rate occurred throughout the pre- and postweaning periods with clearly demarcated phases of growth. Male and female growth in the preweaning period was uniform within each litter type but the phasic growth changes in the experimental litters differed from the control litters with regression line breakage emerging at different points and altering the phasic lengths. The preweaning phasic spectrum in both control and experimental litters was evidently linked to the maternal lactation capacity--relative to quantity and duration. Weaning was insidious in both litter types but occurred earlier in the experimental litters although the continuity of growth was maintained up to the end of the definitive preweaning period (day 20). The definitive postweaning period (day 21-40) showed considerable heterogeneity--unsatisfactory scatter--with differing regression line breakage points and phasic lengths. Analysis based on the total period (day 1-40) brought compensatory adjustments and indicated more acceptable phasic patterns in the postweaning period with confirmation of catch-up growth in the experimental litters. Allometric analysis of the parameters revealed varying rates of growth, line breakage points and differing phasic lengths indicating that each neurocranial parameter and the skeletal unit forming it had an individual characteristic response spectrum mostly attributable to the functional matrix with emphasis on the capsular rather than the periosteal.     

Correlated responses of growth traits to selection for high and low plasma alkaline phosphatase in mice

Summary The effectiveness of two way selection for plasma alkaline phosphatase (ALP) was investigated in order to determine its influences on growth traits through thirteen generations. The responses of the two lines selected for high (HP) and low (LP) ALP at 45 days of age were compared to that of the mice selected for large (L) and small (SM) body size. The selection responses of plasma ALP were very effective for both HP and LP lines, with average responses per generation calculated from linear regressions of 0.227±0.037 and –0.088±0.022 respectively. The final levels of ALP in HP and LP were 5.54±0.71 and 1.27±0.20 in the thirtheenth generation, while the SM, L and base population had levels of 3.49±0.08, 0.86±0.55 and 2.77±0.56 respectively. The body weight at 45 days of age in LP (31.4±1.4 g) as a correlated response was significantly higher than HP (23.4±1.8 g) at generation 10. The correlated response of milk yield, measured by weight gain up to 12 days of age, was significantly greater in the LP line than in HP, but the correlated response of gains after weaning was not so different as the response of milk yield. The response of litter size and weight in LP showed significant higher levels than that of HP, but pups' birth weight did not differ between LP and HP. It is suggested that the correlated response of milk yield contributed more to the divergence of body size between HP and LP than the gain after weaning.Realized heritabilities of ALP were 0.335±0.059 (HP) and 0.279±0.051 (LP). Realized genetic correlations between ALP and 45 days' body weight were –0.27±0.13 (HP with SM) and –0.52±0.19 (LP with L). Realized genetic correlations between ALP and milk yield were –0.95±0.03 (HP) and –0.37±0.29 (LP). Correlations between ALP and postweaning gains were fairly low.     

Crossbreeding effects after long-term selection for purebred performance: a model experiment with mice

Summary The influence of purebred selection on the combining abilities of five lines of mice was examined. Two replicated testcross diallels were made after 10 and 20 generations of purebred selection for litter size, weaning weight, weight gain, and feed efficiency. Average direct genetic effects were of major importance, followed by average maternal genetic effects. In all of the replications, between two and four out of ten crosses showed significant heterosis. Heterosis ranged from 0 to 38% in litter size, from 0 to 20% in weaning weight, from -11 to 11% in weight gain, and from -8 to 17% in feed efficiency. For litter size and weaning weight, heterosis estimates increased between 80 and 100% from generation 10 to 20. Weight gain and feed efficiency showed decreasing heterosis with partly negative estimates in the second diallel. Combinations exhibiting significant heterosis varied between replicates and between the two diallels.     

Milk yield and composition in mice: effects of litter size and lactation number

Milk yield was measured by a tritiated water dilution procedure during consecutive lactations in mice suckling four, 10 or 18 young. Analysis of variance revealed positive effects of lactation number and litter size on milk yield. There was a significant correlation between maternal body weight and parity; increased body weight accounted for some, but not all, of the parity-related increases in milk yield. Peak milk yield was reached between days 10 and 16 of lactation, but the efficiency with which the growing young utilized milk for weight gain was greatest before day 7. Milk composition varied significantly during the course of lactation.     

Growth,feed efficiency and lifetime performance of crosses between lines selected for nursing ability and/or adult weight in mice

Summary Two populations of randombred of different origin (P and Q) containing eight lines (M_P, W_P, B_P, C_P, M_Q, W_Q, B_Q and C_Q) were used to evaluate the growth, feed efficiency and lifetime performance of females from eight pure lines and 16 F₁ crosses. Line comparisons within populations (P or Q) revealed that the heaviest line at days 21, 42 and 63 was W, followed by lines B, M and C in both populations, while the highest in feed efficiency between days 21 and 63 was line W, followed by lines B, M and C in population P, and was line B followed by lines W, M and C in population Q. Generally, average body weights and feed efficiencies of crosses within and between populations were similar to those of mid-parents. Selection produced line W superior to the line M in additive direct genetic effects on body weight and feed efficiency in each population, and line W_P superior to line W_Q in additive maternal genetic effects on body weights at days 21, 42 and 63. In lifetime performance tests, total 20-day weight of litters produced by a dam during 200 days averaged from 442.7 g (W_P) to 739.1 g (M_P) for the eight lines. Lines M and W of populations P and Q generally did not differ in additive direct and maternal genetic effects on lifetime performance. Crosses excelled lines in the number of litters raised to weaning (5.44 vs. 5.25) and total 20-day litter weight per dam during 200 days (648.5 vs. 589.3 g). For lifetime 20-day litter weight per group, crosses from unselected lines (C) exceeded crosses from lines selected for nursing ability (M), adult weight (W) and both traits (B). Crosses of lines from different populations showed a higher heterosis in lifetime performance than crosses of lines within populations. Heterosis in the number of litters raised to weaning, and total 20-day litter weight per dam was significant in crosses between lines C_P and C_Q, between lines W_P and w_Q, and between lines W_P and m_Q. Crosses C_PC_Q and C_QC_P had a highly persistent production during lifetime tests.Animal Research Institute Publication 860USDA SEA-AR, Purdue University, West Lafayette, In. 47906 (USA)     

Effects of dietary enrichment with a marine oil-based n-3 LCPUFA supplement in sows with predicted birth weight phenotypes on birth litter quality and growth performance to weaning

The effects of a marine oil-based n-3 long-chain polyunsaturated fatty acid (mLCPUFA) supplement fed to the sow from weaning, through the rebreeding period, during gestation and until end of lactation on litter characteristics from birth until weaning were studied in sows with known litter birth weight phenotypes. It was hypothesized that low birth weight (LBW) litters would benefit more from mLCPUFA supplementation than high birth weight litters. A total of 163 sows (mean parity=4.9±0.9) were rebred after weaning. Sows were pair-matched by parity and litter average birth weight of the previous three litters. Within pairs, sows were allocated to be fed either standard corn/soyabean meal-based gestation and lactation diets (CON), or the same diets enriched with 0.5% of the mLCPUFA supplement at the expense of corn. Each litter between 9 and 16 total pigs born was classified as LBW or medium/high average birth weight (MHBW) litter and there was a significant correlation (P<0.001) between litter average birth weight of the current and previous litters within sows (r=0.49). Sow serum was harvested at day 113 of gestation for determination of immunoglobulin G (IgG) concentrations. The number of pigs born total and alive were lower (P=0.01) in mLCPUFA than CON sows, whereas the number of stillborn and mummified pigs were similar between treatments. Number of stillborns (trend) and mummies (P<0.01) were higher in LBW than MHBW litters. Tissue weights and brain : tissue weight ratios were similar between treatments, but LBW litters had decreased tissue weights and increased brain : tissue weight ratios compared with MHBW litters. Placental weight was lower (P=0.01) in LBW than MHBW litters, but was not different between treatments. Average and total litter weight at day 1 was similar between treatments. mLCPUFA increased weaning weight (P=0.08) and average daily gain (P<0.05) in MHBW litters, but not in LBW litters. Pre-weaning mortality was similar between treatments, but was higher (P<0.01) in LBW than MHBW litters. IgG concentration in sow serum was similar between treatments and litter birth weight categories. In conclusion, litter birth weight phenotype was repeatable within sows and LBW litters showed the benchmarks of intra-uterine growth retardation (lower placental weight and brain sparing effects). As maternal mLCPUFA supplementation decreased litter size overall, only improved litter growth rate until weaning in MHBW litters, and did not affect pre-weaning mortality, maternal mLCPUFA supplementation was not an effective strategy in our study for mitigating negative effects of a LBW litter phenotype.     

Maternal-care behavior and life-history traits in house mice (Mus domesticus) artificially selected for high voluntary wheel-running activity

To test the hypothesis that selective breeding for high voluntary wheel running negatively affects maternal performance in house mice, we observed maternal behavior and compared litter size and mass, in replicate lines of selected (N=4) and control (N=4) mice from generations 20 and 21 of an artificial selection experiment. At generation 21, selected-line females ran 2.8-times more revolutions per day than females from random-bred control lines, when tested at approximately 6 weeks of age as part of the normal selection protocol. After giving birth, dams from selected and control lines exhibited similar frequencies of maternal behaviors and also spent similar amounts of time in general locomotor activity at litter ages of both 9 and 16 days. Dams from selected lines also performed equally well as controls in repeated pup-retrieval trials. At first parturition, selected-line dams averaged 2.4 g smaller in body mass as compared with dams from the control lines; however, neither litter size nor litter mass at birth (generation 20) or at weaning (generation 21) differed significantly between selected and control lines. We conclude that, at least under the husbandry conditions employed, maternal behavior and reproductive output at first parturition are genetically independent of wheel-running behavior.     

Production and composition of Iberian sow's milk and use of milk nutrients by the suckling Iberian piglet

Sixteen purebred Iberian (IB) sows were used in two consecutive trials to determine the efficiency of conversion of sow's milk into piglet body weight (BW) gain and the relationship between milk protein and body protein retention and between milk energy yield and body energy retention in the nursing IB piglet. In each trial, four sows were selected in order to evaluate their milk production, litter growth and nutrient balance measurements, together with four additional sows for milk sampling. Litter size was equalized to six piglets. Daily milk yield (MY) was determined weekly by the weigh-suckle-weigh technique over a 34-day lactation period. Piglets were weighed individually at birth and then weekly from day 5 of lactation. Milk samples were collected on days 5, 12, 19, 26 and 34 post partum. The comparative slaughter procedure was used to determine piglet nutrient and energy retention. One piglet from each litter was slaughtered at birth and four on the morning of day 35. Total MY was on average 5.175 ± 0.157 kg/day. The average chemical composition (g/kg) of the milk was 179 ± 4 dry matter, 53.4 ± 1.0 CP, 58.5 ± 3.8 fat, 10.4 ± 0.3 ash and 56.9 ± 2.3 lactose. Milk gross energy (GE) was 4.626 ± 0.145 MJ/kg. Milk intake per piglet tended to increase in trial 2 (832 v. 893 g/day; P = 0.066). Piglet BW gain contained (g/kg) 172.1 ± 1.3 protein, 151.5 ± 3.5 fat, 41.4 ± 0.6 ash and 635 ± 3 water and 10.127 ± 0.126 MJ GE/kg. Throughout the 34-day nursing period, the piglets grew at an average rate of 168 ± 3 g/day. The ratio of daily piglet BW gain to daily MY was 0.195 ± 0.002 g/g and the gain per MJ milk GE intake was 41.9 ± 0.5 g/MJ. The overall efficiency of protein accretion (g CP gain/g CP milk intake) was low and declined in trial 2 (0.619 v. 0.571; P = 0.016). Nutrient and energy deposition between birth and weaning were 27.4 ± 0.5 g/day protein, 24.2 ± 0.8 g/day fat and 1615 ± 40 kJ/day energy. Piglet energy requirements for maintenance were 404 kJ metabolizable energy (ME)/kg BW0.75. ME was used for growth with a net efficiency of 0.584. These results suggest that poor efficiency in the use of sow's milk nutrients rather than a shortage in milk nutrient supply might explain the low growth rate of the suckling IB piglet.     

Prenatal versus postnatal effects on offspring weight gain of rats exposed to diphenhydramine: a critical evaluation of fostering procedures in rats.

1. In order to evaluate the relative contribution of fostering procedures in the analysis of the development of rats prenatally exposed to diphenhydramine (20 mg/kg/day, sc) the weight gain of litters fostered or not by their biological mothers were examined from 2-21 days of age. 2. Maternal behavior and milk production were also assessed. 3. The results showed a decreased weight gain only in offspring fostered by mothers from different prenatal treatments and a lack of effects on maternal behavior and milk production. 4. It was concluded that the reduced weight of cross-fostered litters was mediated through an interference with postnatal mother-offspring interaction, which was not herein identified.     

Effects of Population Size and Selection Intensity on Correlated Responses to Selection for Postweaning Gain in Mice

Correlated responses to selection for postweaning gain in mice were studied to determine the influence of population size and selection intensity. Correlated traits measured were three-, six- and eight-week body weights, litter size, twelve-day litter weight, proportion infertile matings and two indexes of reproductive performance. In general, the results agreed with observations made on direct response: correlated responses in the body weight traits and litter size increased as (1) selection intensity increased and (2) effective population size increased. Correlated responses in the body weight traits and litter size were positive in the large population size lines (16 pairs), as expected from the positive genetic correlation between these traits and postweaning gain. However, several negative correlated responses were observed at small population sizes (one and two pairs). Within each level of selection intensity, traits generally associated with fitness tended to decline most in the very small populations (one and two pairs) and in the large populations (16 pairs) for apparently different reasons. The fitness decline at the small effective population sizes was attributable to inbreeding depression. In contrast, it was postulated that the fitness decline at the large effective population size was due to selection moving the population mean for body weight and a trait positively correlated genetically with body weight (i.e., percent body fat) away from an optimum.     

Developmental toxicity of orally administered 2',3'-dideoxycytidine in mice

2',3'-Dideoxycytidine (DDC), a potent inhibitor of human immunodeficiency virus (HIV), is presently undergoing clinical trials as a promising anti-AIDS drug. Since there are very limited published animal toxicity data available, and nucleoside analogues are being considered for treatment of HIV-infected pregnant women, a study was conducted in mice to investigate the potential adverse developmental effects of this drug. DDC, suspended in 0.5% methyl cellulose, was administered via gavage twice per day during gestation days (gd) 6 through 15 to C57Bl/6N mice in a total dose of 0, 200, 400, 1,000, or 2,000 mg/kg/day. Maternal weight gain during the gestation and treatment period, as well as gravid uterine weight, decreased significantly in the 2,000 mg group, but weight gain, corrected for gravid uterine weight, was not affected by DDC. The percent resorptions per litter increased significantly in the highest dose group, and there were fewer live litters because of complete litter resorption in six dams. Among litters with live fetuses, the mean litter size was significantly reduced in the 2,000 mg group. Average fetal body weight per litter decreased significantly in the 1,000 and 2,000 mg groups. The number of fetuses with any malformation, the number of litters with one or more malformed fetuses and the percent of malformed fetuses per litter increased significantly in the 1,000 and 2,000 mg groups. There was an increase in malformations at 400 mg/kg/day; however, it was not statistically significant. In conclusion, DDC produced developmental toxicity (malformations, reduced fetal body weight, and resorptions) in the absence of overt maternal toxicity except for body weight changes due to resorptions and reduced fetal weights.     

Crossbreeding effects after long-term selection for purebred performance: a model experiment with mice

Summary Results are presented from two replicated three-breed cross diallels that were conducted after 20 generations of selection for purebred performance in mice. The selection criteria for the different lines were: litter size at birth (LS), weaning weight at 4 weeks (WW), weight gain from week 4 to week 6 (WG), and body fat content at week 6 (FT). Additionally, a random-mating control line (C) was kept. Significant maternal heterosis was found in litter size and weaning weight. Estimates of maternal heterosis in litter size were very high, ranging from 17 to 50% of the mean of the corresponding single crosses. Maternal heterosis in weaning weight usually was negative and ranged from +9 to -11%. Significant maternal heterosis in feed efficiency and weaning weight could only be found in a few cases. Total performance of three-breed crosses was highly superior to that of single crosses and purebreds. Means of the corresponding purebreds or single crosses were of little use in predicting three-breed cross performance.