An understanding of inbreeding and inbreeding depression are important in evolutionary biology, conservation genetics, and animal breeding. A new method was developed to detect departures from the classical model of inbreeding; in particular, it investigated differences between the effects of inbreeding in recent generations from that in the more distant past. The method was applied in a long-term selection experiment on first-litter size in mice. The total pedigree included 74 630 animals with B30 000 phenotypic records. The experiment comprised several different lines. The highest inbreeding coefficients (F) within a line ranged from 0.22 to 0.64, and the average effective population size (N e ) was 58.1. The analysis divided F into two parts, corresponding to the inbreeding occurring in recent generations ('new') and that which preceded it ('old'). The analysis was repeated for different definitions of 'old' and 'new', depending on length of the 'new' period. In 15 of these tests, 'new' inbreeding was estimated to cause greater depression than 'old'. The estimated depression ranged from À11.53 to À0.79 for the 'new' inbreeding and from À5.22 to 15.51 for 'old'. The difference was significant, the 'new' period included at least 25 generations of inbreeding. Since there were only small differences in N e between lines, and near constant N e within lines, the effect of 'new' and 'old' cannot be attributed to the effects of 'fast' versus 'slow' inbreeding. It was concluded that this departure from the classical model, which predicts no distinction between this 'old and 'new' inbreeding, must implicate natural selection and purging in influencing the magnitude of depression.

Forty-eight Holstein cows, entering second or later lactation, were utilized to determine the effects of 2-hydroxy-4-(methylthio)-butanoic acid (HMB) on milk production, hepatic lipid metabolism, and gluconeogenesis during the periparturient period. Cows were fed one of 3 diets as TMR starting 21 d before expected calving. These diets contained 0 (the basal diet), 0.09 (+HMB), or 0.18 (++HMB)% HMB. From parturition to 84 DIM, cows were fed diets that contained 0, 0.13, or 0.20% HMB. Prepartum and postpartum dry matter intakes were similar among cows fed the basal diet, +HMB and ++HMB. There was a quadratic effect on milk yield such that cows fed +HMB had the greatest milk yield; yields of milk by cows fed the basal diet and ++HMB were similar. This led to trends for increased yields of 3.5% fat-corrected milk and total solids when cows were fed +HMB. Percentages of fat, protein, and total solids in milk were not affected by treatment. Despite differences in milk yield, calculated energy balance was not affected by treatment. Plasma concentrations of NEFA, beta-hydroxybutyrate, and glucose were not different among treatments. Liver triglyceride content was similar among treatments on d 1 postpartum and was increased for cows consuming +HMB on d 21 postpartum compared with the other dietary treatments. Capacities for metabolism of [1-14C]palmitate by liver slices in vitro were not affected by treatment; however, conversion of [1-14C]propionate to CO2 and glucose decreased as the amount of HMB consumed by cows increased on d 21 postpartum. Cows consuming +HMB had greater days to first ovulation compared with cows consuming the basal diet and ++HMB as measured by plasma progesterone concentrations. These data suggest that adding HMB to low Met diets to achieve a predicted Met supply of approximately 2.3% of metabolizable protein supply is beneficial for increasing milk production but does not appear to benefit hepatic energy metabolism during early lactation.

Data on mice selected for litter size over 122 generations have been analysed in order to reveal the effect of long-term selection on responses and changes in variances over a long selection period. Originally, three lines were established from the same base population, namely an H line selected for large litter size, an L line selected for small litter size and a K line without selection. In generation 122, the mean number of pups born alive (NBA) was 22 for the H line and 11 for the K line. Phenotypic response to selection is reduced over generations, but crossing of plateaued lines increased responses and realized heritabilities. Both realized heritabilities and heritabilities from residual maximal likelihood (REML) analyses were, in general, calculated from generation (-1)-44 (period 1), 45-70 (period 2) and 71-122 (period 3) separately. Realized heritabilities were in general smaller than heritabilities estimated from mixed model analysis. An overall estimate of heritability for NBA was found to be 0.19 (+/- 0.01) by REML analysis. Additive variance is constant over all periods in the high line and the control line, but is reduced over periods in the low line. The reduction of additive variance in the low line could probably be explained by changes in gene frequencies. In all lines, environmental variances increased over periods. Inbreeding reduced the mean litter size by 0.72 (+/- 0.10) pups per 10% increase in inbreeding, with substantial variance between periods and lines.

The aim of the present study was to evaluate how ovulation rate and survival rate through pregnancy had been affected by more than 110 generations of upwards selection on litter size in mice. The mean number of pups born alive was 22 in the high line (selected line) and 11 in the control line (an increase in 2.6 standard deviations). Selection on litter size increased ovulation rate by 4.6 standard deviations, and it is suggested that selection also increased embryonic mortality in late pregnancy. Embryo survival from ovulation until birth was 66% in the selected line and 69% in the control line, and the observed loss in litter size from day 16 of pregnancy until birth was possibly higher in the high line compared with the control line. Selection for higher litter size has significantly increased body weight in both males and females, as the mean weight at mating for the females was 46 g in the high line and 33 g in the control line respectively.

We evaluated 2 strains of mice for their utility in the investigation of nutritional and molecular regulatory mechanisms of lactation. The lactational performance and milk composition were characterized for an inbred mouse strain, inbred Quackenbush Swiss line 5 (QSi5) selected persistently for fecundity, and a nonselected strain, CBA. The milk yield assessed by changes in BW in response to suckling of sustainable litter sizes for each strain was 3-fold greater (P < 0.001) in QSi5 mice than the CBA strain. The QSi5 mice also produced milk more efficiently (P < 0.001) than CBA mice, despite having the same quantity of mammary tissue per unit of BW. Milk composition did not vary between strains or by stage of lactation, with the exception of lactose concentration, which was greater (P = 0.003) in QSi5 mice. Expression of epsilon-casein was > or = 10-fold greater, and alpha(S1)-casein was > or = 3-fold greater, during mid and late lactation compared with early lactation in both strains, whereas kappa-casein underwent an apparent alteration in posttranslational modifications in both strains from early to mid lactation. Changes in casein composition coincided with an increased susceptibility to proteolytic degradation; hence milk from early lactation may be more readily degraded to facilitate digestion in the neonate. The greater milk synthetic capacity of QSi5 mice over the lactation cycle provides a useful model for studies of nutritional and molecular regulation of lactation.