Maturing patterns of organ weights in mice selected for rapid postweaning gain

Summary Correlated responses to selection for increased 3–6 week postweaning gain in male mice were estimated for seven internal organs (testes, spleen, liver, kidneys, heart, small intestine (S intest) and stomach) weighed at specific degrees of maturity in body weight (37.5, 50.0, 62.5, 75.0, 87.5 and 100%). Correlated responses in organ weights were generally large, but the magnitude and direction of response depended upon whether 1) comparisons were made at the same age, degree of maturity or body weight and 2) absolute or proportional organ weights were used. The selected line (M16) weighed more and had larger organ weights than controls (ICR) when compared at either the same degree of maturity or the same age, indicating positive genetic correlations between body weight and the respective organ weights. Positive correlated responses were found in spleen weight/body weight at all degrees of maturity and in liver and S intest weights as a proportion of body weight at some degrees of maturity. Testes, kidneys, heart and stomach weights as a proportion of body weight had negative correlated responses, though this was consistent only for kidneys across all degrees of maturity. Correlated responses in organ weights adjusted for body weight by covariance analysis were positive for spleen, S intest and stomach and negative for testes and kidneys. Based on the constrained quadratic model, degree of maturity in organ weight relative to degree of maturity in body weight responded positively for testes, kidneys and S intest and negatively for spleen and liver. Selection for increased growth caused negative correlated responses in allometric growth of testes, kidneys, S intest and stomach.Paper No. 10,545 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 criticism of similar ones not mentioned     

Genetic analysis of nurse dams selected for six-week body weight or postweaning gain in mice.

A modified crossfostering technique was developed to compare the performance of nurse dams in selected and control populations of mice. The H6 and M16 populations were selected for increased 6-week body weight and 3- to 6-week postweaning gain, respectively, while the C2 and ICR populations were the respective controls. Crossfostering was performed using H6, M16 and their reciprocal F1 crosses as nurse dams in the selected crossfostering group and C2 ICR and their reciprocals in the control group. Measurements recorded for nurse dams included mean body weight of 8 young within a nursed litter at birth (MWB) and 12 days of age (MW12). The latter was used as a measure of postnatal maternal performance. Other traits recorded for nurse dams were number born (NB), body weight at parturition (DWP) and 12 days postpartum (DW12), and weight gain (DWG), feed intake (FED) and efficiency (EFF = DWG/FED) for the first 12 days of lactation. The correlated response in MW12 was negative (P less than .01) for M16 and essentially zero for H6. Both lines exhibited positive (P less than .01) correlated responses in DWP and DW12 and no change in EFF. Only the H6 line increases significantly in DWG and FED as a result of selection. NB increased in M16 and H6, but was significant for the latter population only. Population differences in selection response [(M16-ICR)-(H6-C2)] were significant for FED only, primarily due to average direct genetic effects. Direct comparisons of M16 and H6 indicated that M16 was larger in DWP and DW12 but smaller in DWG and EFF. Average direct genetic effects favored M16 for NB, DWP, and DW12, whereas average maternal genetic effects favored H6 for NB, DWP, DW12 and FED. Percent direct heterosis, in F1 crosses of selected populations was significant for MW12 (13.7%) ,FED (10.8%) and NB (11.4%). Direct heterosis in F1 crosses of the controls was significant for MW12 (9.4%), NB (6.6%), DWP (3.5%), DW12 (3.3%) and FED (4.4%). The effects of MW12, DWG and metabolic body size (MBS) accounted for 47% of the variation in FED, pooled within populations. Of these variables, MW12 accounted for the highest proportion (32%) of variation in total feed intake.     

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.     

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.     

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.     

Genetic-statistical analysis of growth in selected and unselected mouse lines

The growth of males sampled from two mouse lines long-term selected for over 86 generations on body weight (DU6) or on protein amount (DU6P) was analysed from birth till 120 days of age and compared to the growth of an unselected control line (DUKs). Animals from the selected lines are already approximately 40 to 50% heavier at birth than the controls. This divergence increases to about 210 to 240% at the 120 day of age. With birth weights of 2.2 and 2.4 g and weights of 78 and 89 g at the 120 day these selection lines are the heaviest known mouse lines.

The fit of three modified non-linear growth functions (Gompertz function, Logistic function, Richards function) was compared and the effect of three different data inputs elucidated. The modification was undertaken to use parameters having a direct biological meaning, for example: A: theoretical final body weight, B: maximum weight gain, C: age at maximum weight gain, D (only Richards function): determines the position of the inflection point in relation to the final weight. All three models fit the observed data very well (r² = 0.949–0.998), with a slight advantage for the Richards function. There were no substantial effects of the data input (averages, single values, fitting a curve for every animal with subsequent averaging the parameters).

The high growth of the selected mice is connected with very substantial changes in the final weight and in the maximum weight gain, whereas the changes of the age at the point of inflection were, although partially significant, relatively small and dependent on the model used.     

Different structures of selected and unselected araB-lacZ fusions

Formation of araB-lacZ coding-sequence fusions is a key adaptive mutation system. Eighty-four independent araB-lacZ fusions were sequenced. All fusions carried rearranged MuR linker sequences between the araB and lacZ domains indicating that they arose from the standard intermediate of the well-characterized Mu DNA rearrangement process, the strand transfer complex (STC). Five non-standard araB-lacZ fusions isolated after indirect sib selection had novel structures containing back-to-back inverted MuR linkers. The observation that different isolation procedures gave rise to standard and non-standard fusions indicates that cellular physiology can influence late steps in the multi-step biochemical sequence leading to araB-lacZ fusions. Each araB-lacZ fusion contained two novel DNA junctions. The MuR-lacZ junctions showed‘hot-spotting’according to established rules for Mu target selection. The araB-MuR and MuR-MuR junctions all involved exchanges at regions of short sequence homology. More extensive homology between MuR and araB sequences indicates potential STC isomerization into a resolvable four-way structure analogous to a Holliday junction. These results highlight the molecular complexity of araB-lacZ fusion formation, which may be thought of as a multi-step cell biological process rather than a unitary biochemical reaction.     

The activity of certain enzymes in the liver of mice,selected for weight gain

Summary Examining the weight gains of mice in selected and nonselected lines maintained on a low (10%) and high (20%) protein diet, and of their crossbreds, it was ascertained that the highest values occurred in selected lines maintained on a high protein level and the lowest in crossbreds.Analysing the enzyme activity — aldolase, aminotransferase AspAT and AlAT — in the liver of these animals, it was observed that selected mice maintained on either of the protein levels demonstrated usually values significantly lower than for the nonselected ones.     

Changes in growth,appetite, food conversion efficiency and body composition in mice selected for high post-weaning weight gain on restricted feeding

Summary This study aimed to test the hypothesis that if animals were fed the same amount over the same time period, selection of the fastest growers would result in a change in the partitioning of metabolisable energy toward more protein and less fat deposition. Two mouse lines (S1 and S2) were selected for high 5 to 9 week weight gain corrected to mean 5 week weight. Appetite variation between mice was eliminated by feeding a fixed amount to each mouse daily. After 6 generations of selection, the lines were compared with an unselected control (C) on restricted and ad libitum levels of feeding for growth rate, appetite, food conversion efficiency and chemical body composition.Realised heritabilities of 5 to 9 week gain were 0.36+ 0.05 and 0.19±0.04 for S1 and S2 respectively. Nine week weights were increased by an average of 13% on both feeding levels. Most of this increase, particularly in S2, occurred before 5 weeks and was therefore outside the period of measurement used in selection. On ad libitum feeding, selection increased food intake per unit time by 6% but there was no increase per unit body weight. Food conversion efficiency (gain/food) increased by 12%. Compared with controls at 9 weeks, 3% more of the body weights of selected mice was fat and 1% less was protein. These differences were reduced but were still in the same direction when comparisons were made at the same body weight. Thus the expected change in energy partitioning toward greater protein and less fat deposition in the S lines did not occur.It was concluded that the increased growth and energy retention in the S lines was brought about by a reduction in maintenance requirement. To achieve the desired change in energy partitioning using a similar selection scheme, higher levels of dietary protein should be fed, and some measure of protein deposition rather than growth rate used as the selection criterion.     

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.     

Milk yield in lines of mice selected for growth or maternal ability.

Two experiments were conducted to measure milk yield as a correlated response to selection for increased 12-day litter weight (maternal lines) for 13 generations and increased and decreased body weight gain from 21 to 42 days of age (postweaning gain lines) for 12 to 14 generations. Milk yield was measured from day 6 to day 21 of lactation by separating litters from their dams for 6 h, then weighing litters before and after a 1.5 h suckling period. Average total milk production was 30.3 +/- 0.9 g and 28.6 +/- 1.1 g in maternal and control lines, respectively. This difference was not significant (P greater than 0.05). Differences among gain lines were significant (P less than 0.01) in the second experiment with average production of 44.1 +/- 1.4 g for increased gain lines, 22.5 +/- 0.9 g for the decreased gain line and 31.2 +/- 1.0 g for the control. These results indicated that response to selection for increased 12-day litter weight was not associated with increases in milk yield, but sizable changes inmilk yield accompanied bi-directional selection for early postweaning gain.     

Inbred lines of mice derived from long-term growth selected lines: unique resources for mapping growth genes

Lines of mice selected for many generations for high or low growth in several laboratories around the world have been collected, and from these, inbred lines are being developed by recurrent full-sib mating in Edinburgh. There are seven high selected lines and four low lines (each low line is from the same base population as one of the high lines), and the histories of each are summarized. Mean body weight of males at 70 days of age in the Edinburgh laboratory in the heaviest inbred line (77 g) is 4.8-fold higher than in the lightest line (16 g), and 1.9-fold higher than in the least extreme high line (41 g). Litter size, food intake, and fat content also differ substantially. These inbred extreme selected lines are a uniquely valuable resource for QTL or gene mapping, candidate gene identification, and elucidation of epistatic effects. Received: 19 February 2001 / Accepted: 3 May 2001     

Body growth and substrate partitioning for fat and protein gain in weaned BALB/c mice treated with growth hormone

Previously we have found that recombinant human growth hormone (rhGH) (GH; 74 ng g body wt.(-1)) administration to weaned BALB/c male mice (fed 12% or 20% protein diet) induced a growth lag and subsequent repletion similar to the catch-up growth process. We studied the partitioning of feed and protein intakes between adipose and protein body stores through the linear relationships among them. The non-linear relationship of protein intake with body fat gain/protein gain (FG/PG) ratio was especially adequate in determining the partitioning of substrates. rhGH induced an increase in feed and protein intake utilization for body weight gain (50%) and fat gain (75-140%) over saline; macronutrient utilization was the greatest in rhGH-treated mice fed 20% protein. However, growth recovery of rhGH mice was anomalous and protein intake was derived primarily for fat gain. Mice fed 12% protein (treated and control) also derived protein intake in preference to fat stores. Treatment and diet had a cumulative effect with the result that rhGH-treated animals fed 12% protein showed the greatest FG/PG ratio (1.6), and therefore, the lowest efficiency to gain protein. Weaning is a critical stage in mice when treating with rhGH, as this could provoke a growth lag. The study showed that a high protein level is required to surpass the rhGH-induced lag, but it is not enough to obtain an enhanced protein deposition. Feeding a 12% protein diet was even worse as mice did not improve on the growth lag and substrates were directed mainly to body fat.