Growth and body composition changes in mice selected for high post-weaning weight gain on two levels of feeding

Summary Two lines of mice were selected for high post-weaning weight gain (3 to 6 weeks) adjusted for 3 week weight. One line (F) was grown on freely available food and the other (S) on a feeding scale set at the same level for all mice. Food intake of the S line averaged 80% of the F line. The realised heritabilities after 6 generations of selection were 0.38±0.06 and 0.33±0.07 for the F and S lines, respectively. In generation 7, mice from the F and S lines and from an unselected control line (C) were compared on both free and set levels of feeding from 3 weeks to 9 weeks of age. Measurements taken were growth rate, appetite, food conversion efficiency (weight gain/food intake) and body composition (fat, protein, ash, water). The F and S lines grew more rapidly and efficiently than the C line on both levels of feeding, each line performing best on the level of feeding on which it was selected. The average genetic correlation between growth rates of the same line on the two feeding levels was 0.54±0.10. The F line grew 19% faster and was 9% more efficient than the S line on free feeding but the S line grew 15% faster and was 15% more efficient than the F line on set feeding. Relative to the C line, food intake per day on free feeding was 4% higher in the F line and 6% lower in the S line. There was no difference between the lines in food intake/g body weight. The rate of deposition of all body components increased in both selection lines. In the F, S and C lines respectively, efficiencies of gains in body components (10²x gain/food) were 1.79, 1.31 and 1.06 for fat, 1.53, 1.63 and 1.22 for protein and 5.88, 6.45 and 4.98 for protein + water. Apparently energy lost as heat was reduced in both the F and S lines. The partitioning of energy retained was altered in favour of more fat in the F line and more protein in the S line.     

Heterosis among lines of mice selected for body weight

Summary To examine the effect of selection on levels of heterosis, crosses were made between three groups of six lines of mice, one group unselected (controls) and the other two selected for high (large lines) and low (small lines) 6-week body weight, respectively. The coefficient of inbreeding of each line was about 0.60. Each line was crossed reciprocally to one line from each of the parental groups, as well as producing purebred progeny. Heterosis for 3-week weight, 6-week weight and 3–6 week gain averaged 0.0%, 2.4% and 4.2%, respectively, and was higher for males than for females. Heterosis was more extensive in crosses involving large or control lines than in crosses with small lines. There was no detectable heterosis in several measures of developmental rate, such as age at vaginal opening. Food conversion efficiency and carcass composition were measured on a sample of the animals. Food consumption, gonadal fat pad weight, and hindquarters weight, each expressed as a proportion of body weight, exhibited –4.0%, 5.6%, and 2.3% heterosis, respectively.     

Direct and maternal genetic effects on body weight maturing patterns in mice

Summary Direct and maternal genetic effects were evaluated for maturing patterns of body weight in mice using a crossfostering design. Crossfostering was performed in one group using dams from populations selected for rapid growth rate (M16 and H₆) and their reciprocal F₁. crosses. A second crossfostering group consisted of dams from the respective control populations (ICR and C₂) and their reciprocal F₁. 's. Population differences were partitioned into direct and maternal effects due to genetic origin, correlated selection responses, heterosis and cytoplasmic or sex-linked effects. Degree of maturity was calculated at birth, 12, 21, 31 and 42 days of age by dividing body weight at each age by 63-day weight. Absolute and relative maturing rates were calculated in adjacent age intervals between birth and 63 days. Genetic origin effects (ICR vs. C₂; M16 vs. H₆) were significant for many maturity traits, with average direct being more important than average maternal genetic effects. In general, correlated responses to selection for maturity traits were larger in the M16 population (M16 vs. ICR) than in the H₆ population (H₆ vs. C₂) and correlated responses in average direct effects were larger than average maternal effects. Positive correlated responses in average direct effects were found for relative maturing rates at all ages and for absolute maturing rates from 31 to 63 days. Apparent correlated responses in degree of maturity were negative for M16 and H₆. However, further analysis suggested that the correlated response for degree of maturity in H₆ may be positive at later ages and negative at earlier ages. Direct and maternal heterosis for degree of maturity was positive in the selected and control crosses. Absolute and relative maturing rates showed positive heterosis initially, followed by negative heterosis. Reciprocal differences due to the cytoplasm or sex-linkage were not important for patterns of maturity.Paper No. 5244 the Journal Series of the North Carolina Agricultural Experiment Station, Ealeigh, Animal Research Institute Contribution No. 683 and Agricultural University at Wageningen Contribution No. 654–490–12On leave from the Animal Research Institute, Agriculture Canada at Ottawa, OntarioOn leave from the Department of Animal Husbandry, Agricultural University at Wagenitgen, the Netherlands     

Feed efficiency and body composition of selected and unselected mice

Summary An examination was carried out of the feed intake, feed efficiency and body composition of selected and unselected mice. It was demonstrated that selected mice utilised food more economically, and, in total, produced more protein than the control animals. However, selection had a negative influence on the percentage content of protein and ash. Also, selection caused greater adiposity of selected females and a greater water content in the bodies of selected males (in %).This work was partly supported by grant No. FG-Po-348 (JB-13), Project No. PL-ARS-68.     

Selection for components related to body composition in mice: correlated responses

Summary Correlated responses were estimated in each of two replicate lines of mice selected within full-sib families for high (HF) or low (LF) 12-week epididymal fat pad weight as a percentage of body weight (epididymal fat pad percentage), or high (HL) or low (LL) 12-week hind carcass weight as a percentage of body weight (hind carcass percentage). Two replicate control lines (RC) were maintained. Correlated traits were measured in each of the 10 generations of selection. Realized (r_{G R}) and offspring-sire genetic correlations generally were in agreement. In HF and LF, 3–6 week postweaning gain (r_{G R} = 0.36±0.04) and feed intake (r_{G R} = 0.50±0.13) had positive correlated responses, but feed efficiency and feed intake/metabolic body size did not change. Positive correlated responses were found for subcutaneous fat pad percentage, body weight-adjusted subcutaneous fat pad weight and fat percentage in the hind carcass (r_{G R}'s were 1.04±0.13, 0.93±0.13 and 0.90±0.08). In the hind carcass, fat-free dry (protein + ash) percentage showed a small negative correlated response, and fat-free dry weight did not change. In HL and LL, the correlated responses for the above traits were generally opposite to those observed in HF and LF. Litter size, percentage of infertile matings, and preweaning mortality showed no consistent correlated responses in any of the lines, but an index of fitness combining the three traits showed a decrease in all four selection treatments.Paper no. 11057 of the Journal Series of the North Carolina Agricultural Research Service, Raleigh, 27695-7601. The use of trade names in this publication does not imply endorsement by the North Carolina Agricultural Research Service of the products named, nor criticisms of similar ones not mentioned     

Chiasma frequency in strains of mice selected for litter size and for high body weight

Summary Chiasma frequency was measured in male mice of three outbred lines: FZt:DU (control); DU:6, selected for increased body weight; and DU:C, selected for high fertility. Chiasma frequency was seen to increase in the high body weight line, but decrease in the high fertility line. In both selected lines the intragroup variance in chiasma frequency increased while in DU:C the intracell variance was lower than in the control.     

Correlated responses in development and distribution of fat depots in mice selected for body composition traits

Summary Development of adipose tissue in five depots was investigated in mice selected for high or low 12-week epididymal fat pad weight as a percentage of body weight (HF and LF lines), or high or low 12-week hind carcass weight as a percentage of body weight (HL and LL lines). An unselected control line (RC) was maintained. Hind carcass (HC) and fat pads from subcutaneous hindlimb, subcutaneous forelimb, gonads, kidneys and mesentery were dissected and weighed at 4, 6, 9, 12 or 15 weeks of age. Generally, body weight (BW), daily gain (DG), feed intake (FI), feed efficiency (FE) and feed intake/metabolic body weight (FC) were higher (P0.05) in HF than in LF, and in LL than in HL. HF had more fat (as a percentage of BW) than LF in all depots (P-0.01), and asymmetry (P0.01) was detected for gonadal fat. LL consistently had a higher (P0.01) fat percentage than HL, and asymmetry (P0.01) was observed for perirenal fat. At age of selection, ranking of fat depot weights as a percentage of total fat depot weight was not changed by selection; however, gonadal fat accounted for more of the total fat in HF and LL compared with RC, while the opposite was found in LF and HL. HC percentage was higher (P0.01) in HL than LL, and higher (P0.01) in LF than HF. Growth rate of each fat depot relative to BW was not affected by selection. These results demonstrated that selection for proportion of fat in one depot or for HC percentage changed fat percentage in other depots. However, the rate of fat deposition in each depot relative to body weight gain was not altered.     

The relative importance of prenatal and postnatal maternal influences on growth in mice

Summary The cross-nursing technique was used to assess the relative importance of prenatal and postnatal maternal influences on growth in mice from an unselected population originated from a cross of four highly inbred strains. Body weights were studied at birth, 7-, 14-, 21- and 42-days, in addition to the weight gains between these ages and tail length at 21 and 42 days of age. At littering, each dam in each nursing set retained two of her own offspring and two were transfereed to each of the other dams in the set, so that each nursed litter contained six young representing three mothers. Prenatal influences accounted for 37, 15, 10, 11 and 13 % of the total variation in the respective body weights, while postnatal influences accounted for 0, 64, 65, 49 and 14% at the respective ages. In the case of weight gains, prenatal influences were responsible for 16, 4, 6 and 30%, while postnatal influences were responsible for 66, 66, 31 and 7% of the total variation in gain during the respective four periods examined. Apparently the individual weight gain from 7 to 14 days was a better measure of the lactational performance of the dam than individual 14-day weight. For tail length, prenatal influences accounted for 6 % and 4 % of the total variation in tail length at 21 and 42 days, respectively, while postnatal influences accounted for 60 % and 24 % at the respective ages. Generally, there was no indication of an important interaction between the nurse and the nursed young at any stage studied.     

Energy expenditure and locomotor activity in mice selected for food intake adjusted for body weight

Summary The aim of this study was to examine the differences in physical activity and their contribution to differences in energy utilization in mice, selected either high or low for food intake, adjusted for body weight, which show correlated responses in lean content and metabolic rate. Simultaneous measurements of fasting metabolic rate and activity were made in lines of mice selected at either: a young age, 4-to 6-week food intake corrected for 4-week body weight; or an older age, 8- to 10-week food intake corrected for mean weight at 8 and 10 weeks of age. Correlated response in metabolic rate was found to have been accompanied by changes in locomotor activity near the ages at selection in both sets of lines. Activity, however, accounted for only a small proportion of variation in fasting heat production, generally less than 5%, although a highly positive correlation (r=0.63) between the two traits was found. It was concluded that selection for food intake adjusted for body weight has led to correlated response in physical activity. In consequence, mice selected in the upward direction expend some of the excess energy intake rather than assimilating it as body mass and are, therefore, slightly leaner than their counterparts selected in the downward direction.     

Direct and correlated responses to selection for weaning weight,post-weaning weight gain and six-week weight in mice

Summary Four lines of mice were formed from a common base population and selected for 37 generations for either increased 3-week weight (weaning weight), 6-week weight, 3–6 week gain, or maintained as a randomly bred control line. Realised heritability estimates for short-term (long-term) responses were 0.33±0.20 (0.07±0.10), 0.46±0.14 (0.26±0.09), 0.36±0.14 (0.24±0.11) for 3-week weight, 6-week weight and 3–6 week gain, respectively. Realised genetic correlations estimated from short-term (long-term) responses were 0.23±0.08 (0.35±0.10) between 3-week weight and 3–6 week gain; 0.82±0.04 (0.58±0.08) between 3-week weight and 6-week weight; and 0.81±0.04 (0.97±0.04) between 3–6 week gain and 6-week weight. The genetic correlation between 3-week weight and 6-week weight was asymmetric with a greater correlated response for 3-week weight when selecting for 6-week weight (1.06) than vice versa (0.63).     

Age-related body weight constraints on prenatal and milk provisioning in Iberian red deer (Cervus elaphus hispanicus) affect allocation of maternal resources

Maternal phenotypic characteristics can influence key life history variables of their offspring through maternal effects. In this study, we examined how body size constraints on maternal weight in yearling and subadult compared to adult hinds (age class effects) affected prenatal (calf birth weight, calf to hind weight ratio) and postnatal (milk) provisioning of Iberian red deer calves. Age correlated with all prenatal and postnatal investment traits except calf gains, although correlations were weaker than those with maternal weight. Once the effect of linear increase in weight with age was removed from models, yearlings showed additional reductions in calf birth weight, calf gains, and milk provisioning. The low-calf birth weight might increase the risk of calf mortality during lactation, as this occurs primarily during the first day of life and is strongly related to birth weight. Yearlings showed a greater prenatal allocation of resources in terms of greater calf to hind weight ratio probably as an extra effort by yearling mothers to balance calf neonatal mortality. It might compensate young mothers to produce low-quality calves while still growing rather than waiting for the uncertain possibility of surviving to the next reproductive season.     

The effects of selection for gain in mice on the direct-maternal genetic correlation

Components of genetic variation for postweaning growth traits were estimated for both control and growth stocks of mice. The effect of phenotypic selection for gain, which genetically combines selection for additive direct and maternal effects, on additive genetic variance components, heritability, and additive genetic correlationsis discussed. Quantitative genetic theory predicts that simultaneous selection for two metric traits in the same direction will cause the genetic correlation between the two traits to become more negative. The results presented in this paper conflict with this theory. The direct-maternal additive genetic correlation was more negative in the control line (with 356 mice) than in the growth-selected line (with 320 mice) for the three traits analyzed (0.310 vs 0.999 for 21-day weight, 0.316 vs 1.000 for 42-day weight, and 0.506 vs 1.000 for gain from 21–42 days). Estimates were obtained by restricted maximum likelihood (REML) computed under a derivative free algorithm (DFREML).     

Direct genetic and postnatal maternal genetic effects on body composition in mice selected for body weight.

Line crossfostering techniques were used to study differences among selected and control lines of mice in direct genetic and postnatal maternal genetic influences on preweaning (day 12) body weight and composition. The lines were selected for high (H6) and low (L6) 6-week body weight and the control line (C2) was maintained by random selection. There were positive correlated responses to selection in both direct genetic and postnatal maternal genetic effects on body weight and weights of all body components (P less than 0.01) except for water and ash weight in H6. The correlated responses in postnatal maternal genetic effects were of the same order of magnitude as those in direct genetic effects. Correlated responses were greater in L6 than in H6. Correlated responses in direct genetic effects were positive (P less than 0.01) for water percent in H6 and ether extract percent in L6, and negative (P less than 0.01) for water percent and lean percent in L6. Correlated responses in postnatal maternal genetic effects were positive for ether extract percent and negative for water percent (P less than 0.01). Correlated responses were far greater in L6 than in H6 and were greater for postnatal maternal genetic effects than for direct genetic effects. Analyses of covariance results indicated line differences in the relative growth rates of the body components.     

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.     

Effect of selection for spot size on reproduction and body weight in mice

Summary Spot size in descendants from the Goodale white-spotted stock of mice responded to selection for increased spot size. The realized heritability estimate was 0.52. However, no correlated response of reproduction to spot size selection was found in the present study, nor was there any correlated response among body weight variables.Joint project of Purdue University and USDA-SEA-ARS, North Central Region. Journal paper number 8279 from the Purdue Agricultural Experiment Station     

Growth and body composition of mice selected for high body weight

To elucidate the influence of high body weight selection on body compositional relationships, the accumulation of lipid, protein, and ash was investigated in two lines of mice selected for high 42-day body weight (H lines) and an unselected foundation population (FP). The two H lines differed in population size and were designated as the high-large (HL) and high-small (HS) lines. Logistic body growth curves revealed that HL mice exhibited an accelerated growth rate and reached a higher mature body weight than FP or HS mice. Over the range of body weights examined, HL mice had more lipid, less protein, and less ash than FP or HS mice of the same sex and body weight. However, HL lipid accumulation (relative to body weight increase) was not accelerated in comparison to that of FP mice. This study suggests that the existing model of selection-mediated compositional changes requires expansion to account for the ability of high-growth selection to direct an acceleration of body growth without a correlated enhancement of the relative rate of fat accumulation.     

Decreased frequency of the rat growth hormone transgene in mouse populations with or without selection for increased adult body weight

Summary Frequencies of mice with the rat growth hormone (rGH) transgene were examined in lines derived from two genetic bases (P/W and P/C). The genetic bases were developed from males (P) with the rGH transgene, mated with non-transgenic females of different origin: a line previously selected for large body size (W) and a corresponding unselected control line (C). They were maintained for six generations under random mating with or without selection for increased 42-day body weight. The frequencies of P/W and P/C males with the rGH transgene wer 0.075 and 0.300, respectively at generation 0 of the genetic bases. They were significantly (P<0.05) lower than the expected frequency (about 0.5). At generation 6, the frequencies had decreased further both in selected and unselected lines (ranging from 0.025 to 0.125). Decreased frequencies of mice with the transgene were confirmed in a separate experiment testing segregation of the transgene. The reasons for these decreases are not clear. The results suggest that transgenes need to be monitored when transgenic animals are mated with animals of different origin.Animal Research Centre Contribution No. 1697     

Selection for components related to body composition in mice: direct responses

Summary Replicated within full-sib family single-trait selection was conducted for 10 generations in mice for (1) high or low 12-week epididymal fat pad percentage (100 x epididymal fat pad weight/body weight) or (2) high or low 12-week hind carcass percentage (100 x hind carcass weight/body weight). Pooled realized heritabilities based on high, low and divergent selection were 0.66±0.09, 0.65±0.13 and 0.66±0.05 for epididymal fat pad percentage and 0.48±0.08, 0.33±0.08 and 0.40±0.04 for hind carcass percentage. The pooled realized genetic correlation (r_{G R}) between epididymal fat pad percentage and hind carcass percentage based on divergence was –0.67±0.04. Other estimates of (r_{G R}) were: epididymal fat pad percentage with body weight (0.57±0.05); epididymal fat pad percentage with epididymal fat pad weight (1.17±0.05); hind carcass percentage with body weight (–0.61±0.09); hind carcass percentage with hind carcass weight (–0.05±0.11). Indirect measures of fat and lean tissue percentages were highly heritable, and (r_{G R}) between them would be desirable from the standpoint of analogous types of traits in livestock. In the same context, undesirable (r_{G R})'s were found between epididymal fat pad percentage and body weight and between hind carcass percentage and body weight.Paper No. 10957 of the Journal Series of the North Carolina Agricultural Research Service, Raleigh, North Carolina 27695-7601, USA. The use of trade names in this publication does not imply endorsement by the North Carolina Agricultural Research Service of the products named, nor criticism of similar ones not mentioned     

Direct and correlated responses to selection for post-weaning weight gain on ad libitum or restricted feeding in mice

Summary Selection for post-weaning weight gain in mice from 21 to 42 days, on either a full or restricted feeding level during this period was carried out for seven generations. Control lines were maintained for each feeding level. The rate of selection response was higher on full feeding due to a higher heritability and a larger phenotypic variance. Realised heritabilities of 0.29±0.05 and 0.19±0.04 for selection on full and restricted feeding respectively, were in close agreement with base population estimates.Selection on full feeding led to positive correlated responses in 21 day weight, 42 day weight, food intake and efficiency between 21 and 42 days, and 42 day tail length, but with little change in reproductive performance.Correlated responses to selection on restricted feeding were reduced 21 day weight, but an increase in 42 day weight and increased efficiency from 21 to 42 days. However, overall reproductive performance fell.     

QTLs for pre- and postweaning body weight and body composition in selected mice

In an intercross between the high-body-weight-selected mouse line NMRI8 and the inbred line DBA/2, we analyzed genetic effects on growth during the suckling period and after weaning during the juvenile phase of development. QTL mapping results indicated that a switch of gene activation might occur at the age of three weeks when animals are weaned. We found QTLs for body weight with major effects at the age of two and three weeks when animals are fed by their mothers, and QTLs with highest effects after weaning when animals have to live on their own under ad libitum access to food. Specific epistatic effects on body weight at two and three weeks and epistatic interaction influencing growth after weaning support this finding. QTL effects explained the greatest variance during puberty when animals grow fastest and become fertile. In the present study, all except one QTL effect for early body weight had dominance variance components. These might result from direct single-locus-dominant allelic expression, but also from the identified epistatic interaction between different QTLs that we have found for body weight at all ages. Beside body weight, body composition traits (muscle weight, reproductive fat weight, weight of inner organs) were analyzed. Sex-dimorphic QTLs were found for body weight and fat deposition. The identified early-growth QTLs could be the target of epigenetic modifications which might influence body weight at later ages.