Quantitative genetics of transgenic mice: components of phenotypic variation in body weights and weight gains.

Transgenic mice possessing an ovine growth hormone gene were used to study the effects of elevated growth hormone on quantitative genetic variation. Males hemizygous for the transgene were mated to wild-type females to produce half- and full-sib families in which approximately half the progeny were transgenic and half were wild type. Analyses of body weights at 3-10 weeks, and weight gains from 3 to 6, and 6 to 10 weeks produced estimates of the proportion of total variance due to additive genetic effects (h2) and common litter effects (c2), and the genetic correlation between transgenic and wild-type expression of each trait. At 10 weeks, body weight of transgenics exceeded that of wild types by 26 and 49% in males and females, respectively. Estimated genetic variances in the transgenic group were significantly greater than zero for body weights at most ages and for both measurements of gain. Common litter effects accounted for a similar proportion of variation in the wild-type and transgenic groups. Additive genetic correlations between wild-type and transgenic expression of body weights tended to decline with age, indicating that a partially different array of genes may have begun to affect body weight in the transgenic group.

Plasma cholecystokinin-8 in pigs with divergent genetic potential for feed intake and growth.

Plasma cholecystokinin-8 (CCK-8) was studied in pigs with divergent genetic potential for feed intake. Differences in feed intake resulted from selection for either fast (line F) or slow (line S) postweaning gain. The hypothesis was that the relatively lesser feed intake in S versus F may be attributable, in part, to greater circulating concentrations of the putative satiety hormone CCK-8. In Experiment I, barrows from F (n = 23) and S (n = 19) were used to determine changes in CCK-8 associated with ad libitum feed consumption. Blood samples were collected after overnight feed deprivation, then periodically during a 2-hr feeding period. Averaged across sampling times, concentration of CCK-8 tended to be greater (P = 0.07) in S (6.70 pmol/l) than in F (5.06 pmol/l). Concentration of CCK-8 per unit of feed consumed (CCK-8/cumulative feed intake) was greater (P < 0.01) in S than in F during the first 30 min of the feeding period. In Experiment 2, plasma concentrations were determined for nine pairs (F, S) of the same barrows allowed an amount of feed equal to the previous ad libitum intake of the S barrow in the pair. Averaged across times, the difference between CCK-8 concentrations of S (11.65 pmol/l) and F (7.94 pmol/l) barrows was not significant (P = 0.18). A greater concentration of CCK-8 per unit of feed consumed in S than in F supports the hypothesis that satiety effects of CCK-8 may play a role in genetic differences between the lines for feed intake.

Effect of level of beef cow milk production on pre- and postweaning calf growth.

Three groups of beef cows that were similar in growth and mature size, but different in genetic potential for level of milk provided to their calves, were studied. A procedure for fitting grafted polynomials based on calf suckling data was used to estimate the total amount of milk produced by each cow during 205-d lactations. Estimated 205-d milk production of the high milk group exceeded that of the medium and low milk groups by 186 and 561 kg, respectively. Differences in milk production of the three groups tended to increase as dams got older. The pooled, within milk-group correlation between calf gain to 205 d and milk intake was .60. Calves suckling dams with low milk production relied earlier and to a greater extent on alternative food sources of lower nutritional value than milk. Calves suckling high milk-group dams had 16.9 kg greater 205-d weaning weight than those suckling low milk-group dams, solely because of differences in maternal environment. Calves from the high milk group maintained 63% of the advantage over those in the low milk group in 205-d weight through a fairly rapid postweaning growth period to slaughter.

Effect of divergent selection for postweaning average daily gain on front-end soundness of market-weight pigs.

A total of 975 barrows and gilts from lines divergently selected for postweaning ADG were evaluated for front-end structural soundness (scored on a scale from 1, extreme leg weakness, to 8, superior leg structure) at approximately 100 kg, as well as growth performance and backfat thickness. Selection was for either fast (line F) or slow (line S) ADG from 9 wk of age to 100 kg and was replicated in spring- and fall-farrowing groups. The cumulative divergent selection differential corresponding to the animals evaluated was .47 kg/d (approximately 5 standard deviations). There was a line x sex x farrowing group interaction (P < .05) for ADG. Pigs from F grew faster (P < .01) than pigs from S, but the difference between lines was greater in gilts than in barrows. This interaction between line and sex was more pronounced in the spring- than in the fall-farrowing group. Average daily feed intake was 23% greater (P < .01) for F pigs than for S pigs. Even though pigs from F consumed more feed than those from S, their relatively faster ADG resulted in a greater (P < .01) feed efficiency (gain/feed) in F than in S. There was a line x farrowing group interaction (P < .05) for average backfat thickness adjusted to 105 kg. Barrows and gilts from F had 3.9 and 8.3% greater backfat thickness than those from S in the fall- and spring-farrowing groups, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Uterine capacity and ovulation rate in mice selected 21 generations on alternative criteria to increase litter size.

After 21 generations of selection for alternative criteria to change litter size in mice, responses in uterine capacity and ovulation rate were evaluated. Females from Generations 22 and 23 were sampled from 12 lines, representing three replicates of four selection criteria: LS = direct selection on litter size; IX = selection on an index of ovulation rate and the proportion of ova shed that resulted in fully formed offspring; UT = selection on uterine capacity measured as litter size from females unilaterally ovariectomized at 4 wk of age; and LC = unselected control. All females in the present evaluation (a total of 1,932) were unilaterally ovariectomized (either left or right ovary excised) at 4 wk, mated at 9 wk, and killed at d 17 of gestation. The number of corpora lutea and number of fetuses were counted to measure ovulation rate and uterine capacity, respectively. Selection in IX, LS, and UT increased (P < .01) ovulation rate from unilaterally ovariectomized females but by a greater amount (P < .01) in IX and LS than in UT. Selection also increased (P < .01) uterine capacity of IX, LS, and UT (average response relative to LC = 1.76 pups); response was at least as great in LS and IX as in UT. Direct selection in UT was successful at improving uterine capacity but was no more effective than IX or LS selection. Cases in which ovulation rate limited expression of uterine capacity in UT may have shifted some selection emphasis to ovulation rate and reduced response in uterine capacity.

Estimates of heritabilities and genetic and environmental correlations for left- and right-side uterine capacity and ovulation rate in mice.

Heritabilities for and genetic and environmental correlations between uterine capacity, ovulation rate, and body mass (BM) were estimated in mice. Uterine capacity was defined as the number of fetuses (LUC or RUC for left or right side) in one uterine horn for unilaterally ovariectomized females. Ovulation rate (corpora lutea, LCL or RCL for left or right ovary) was measured on the remaining single ovary in these same females. Data on 1,931 mice from four selection populations were used. Left ovulation rate and LUC were measured on 958 animals, and RCL and RUC of another 972 animals were recorded. Genetic and environmental variances and covariances were estimated simultaneously using an animal model with a multiple-trait, derivative-free, restricted maximum-likelihood procedure. Averages for heritability and correlation estimates derived from separate analyses of the selection populations are presented below. Heritability of LUC was higher (.33 +/- .06) than that of RUC (.19 +/- .02). Heritability of LCL and RCL ranged from .17 +/- .03 to .27 +/- .06, and heritability for BM was .65 +/- .05. The genetic correlation between LUC or RUC and LCL or RCL ranged between .43 +/- .29 and .68 +/- .05, and between LUC and RUC was .92 +/- .05. Body mass had a higher genetic correlation with LCL and RCL (.70 +/- .12 and .93 +/- .02) than with LUC and RUC (.37 +/- .05 and .47 +/- .12). Environmental correlations between LCL and LUC and RCL and RUC were .32 +/- .09 and .36 +/- .05, respectively.

Alternative methods of selection for litter size in mice: I. Characterization of base population and development of methods.

Studies on a base population of mice were used to establish an index of components of litter size and a physiological model for measuring uterine capacity to be used subsequently in a selection experiment evaluating alternative methods for practicing selection to increase litter size. Heritability estimates of litter size, ovulation rate and ova success (fraction of ova resulting in fully formed pups) were .18, .33 and .15, respectively. No significant genetic or phenotypic correlation was found between overall ovulation rate and ova success. Phenotypic means and genetic variances were higher for characteristics measured on the right than on the left side of the reproductive tract. Linear and quadratic selection indexes, derived for a quadratic definition of breeding value, were compared. The linear index was predicted to be .99 as efficient as the quadratic one. Due to simplicity, the linear index (I = 1.21 x ovulation rate + 9.05 x ova success), scaled to have variance the same as litter size, was chosen for use. Ovulation rate in unilaterally ovariectomized females was .95 of that in females with both ovaries. No hypertrophy of the ipsilateral uterine horn in unilaterally ovariectomized females was found before implantation of embryos. Thus, unilateral ovariectomy appears to provide a physiological state to measure uterine capacity (as litter size) in the mouse.

Alternative methods of selection for litter size in mice: II. Response to thirteen generations of selection.

Selection was conducted on an index of components of litter size (I = 1.21 x ovulation rate + 9.05 x ova success; ovulation rate measured by number of corpora lutea and ova success measured as number of pups born + number of corpora lutea), on uterine capacity (measured as number of pups born to unilaterally ovariectomized dams) and on litter size concurrent with an unselected control for 13 generations. Selection criteria (IX = index, UT = uterine capacity, LS = litter size and LC = control) were applied in each of three replicates. In an evaluation after five generations, IX and LS each exceeded LC by about .5 pups, with no response in UT. After 13 generations, mean ovulation rate, ova success and litter size (measured as number of fetuses at 17 d gestation in intact females) were, for IX, 14.25, .84, 11.95; for LS, 14.15, .82, 11.64; for UT, 12.61, .86, 10.77; and for LC, 12.27, .82, 9.98. The regression of number born (litter size in IX, LS and LC; uterine capacity with only a functional left uterine horn in UT) on cumulative selection differential across 13 generations was .12 +/- .01, .09 +/- .02 and .08 +/- .02 for IX, LS and UT, respectively. The regression of breeding value for litter size on each selection criterion, estimated as response in the generation-13 evaluation divided by cumulative selection differential, was .11 +/- .02, .08 +/- .01 and .05 +/- .03 for IX, LS and UT, respectively. Regression of response in number born on generation number was .17 +/- .01, .15 +/- .04 and .10 +/- .02 for IX, LS and UT, respectively. Selection in IX was promising relative to LS, and selection in UT changed number born.

Mapping genomic regions associated with growth rate in pigs.

The objective of this study was to identify genomic regions associated with postweaning average daily gain (ADG) in swine. Two families were produced using sires obtained from the cross of lines divergently selected for high and low growth rate. Sires were mated to 29 unrelated dams that produced 124 and 115 offspring. Average daily gain was recorded for every individual; mean ADG was .593 +/- .007 kg/d and .619 +/- .009 kg/d in the two families. Selective genotyping was performed as a prescreening procedure to identify genomic regions potentially associated with ADG. A total of 75 genetic markers were used between both families. Markers identified as nominally significant (P < .05) in an individual marker analysis were subsequently typed in all individuals. Markers still nominally significant (P < .05) after analysis with the complete family were then reevaluated together with flanking markers in an interval mapping analysis. A single region on chromosome 3, flanked by markers Sw2429 and Sw251, for the second family had a logarithm of the odds score of 2.9, which is suggestive of linkage with a quantitative trait locus for ADG. Differences were .033 +/- .009 kg/d between individuals inheriting alternative paternal alleles for Sw251, which was the most significant marker.

Growth and carcass characteristics of pigs selected for fast or slow gain in relation to feed intake and efficiency.

Selection in pigs for either fast (line F) or slow (line S) postweaning gain was replicated in spring (SREP) and fall (FREP) farrowing groups. Littermate barrows were sampled from F and S during Generations 2, 3, and 4 of the SREP and Generation 3 of the FREP. Beginning at approximately 35 kg (OTWT), barrows were either allowed ad libitum access to feed (AL) or limited to a standard total feed intake (LIM). Blocks of the line x intake level factorial were removed from test and carcass data collected when the average weight of barrows in the block was approximately 110 kg. Carcass data were also collected on an additional barrow from each litter at OTWT to allow estimation of lean tissue gain per unit of feed consumed (LTFC) of tested barrows. In Generations 3 and 4 of the SREP, F-AL was greater (P less than .01) than S-AL for average daily intake and ADG; carcass backfat was greater (P less than .01) but LTFC tended to be less (P less than .10) for F-AL than for S-AL. When LIM was imposed in the SREP, F barrows gained faster (P less than .05) than S barrows in Generation 4, but across generation the lines did not differ for carcass backfat and LTFC was greater (P less than .01) for F than for S. In the FREP, F-AL was greater (P less than .05) than S-AL for average daily intake and ADG and was less (P less than .05) for LTFC, but F and S did not differ for these traits when LIM was imposed; carcass backfat of F was greater (P less than .01) than that of S by .46 cm under AL and .38 cm under LIM. Most of the response in ADG could be attributed to changes in intake, but results in Generation 4 of the SREP indicated that changes in efficiency had also contributed. Most of the additional intake in F vs S resulted in deposition of fat, probably due in part to the heavier weight of F-AL vs S-AL barrows.

Plasma growth hormone, insulin-like growth factor I, and insulin-like growth factor binding proteins in pigs with divergent genetic merit for postweaning average daily gain.

Characteristics of growth hormone (GH), IGF-I, and IGF-binding proteins (IGFBP) were studied in gilts sampled from lines of pigs selected for either fast (line F, n = 14) or slow (line S, n = 14) postweaning ADG. Repeated blood samples were obtained from gilts (approximately 55 kg BW) during a period of feed deprivation and again during refeeding. Averaged across time, the difference in mean plasma GH concentrations of F and S gilts was not significant (7.7 vs 6.4 ng/mL; P > .20) during feed deprivation, and frequently, height, and amplitude of GH pulses did not differ (P > .25) for F and S pigs. Overall, F gilts had greater concentrations of plasma IGF-I than S gilts during feed deprivation (217.3 vs 145.1 ng/mL; P < .03). Across line, plasma IGF-I decreased (P < .01) during feed deprivation. Average GH did not differ (P > .40) for F and S gilts during the refeeding period. Average plasma IGF-I tended (P = .05) to be greater in F gilts than in S gilts during refeeding. Consistent with changes over time during feed deprivation, plasma IGF-I averaged across line increased (P < .01) in response to refeeding. Averaged across time (0 and 48 h refeeding), activity of IGFBP-2 (singlet band at 34 kDa) did not differ significantly (P = .17) in F and S gilts. However, there was a tendency (P = .13) for a line x time interaction.(ABSTRACT TRUNCATED AT 250 WORDS)

Suckling behavior of calves with dams varying in milk production.

Two experiments were performed to test the hypothesis that suckling behavior of calves with similar growth potential varies depending on cows' level of estimated milk production and stage of lactation. Eleven mature cows, which varied in estimated 205-d milk production (996 to 2354 kg/205 d), nursing heifer calves of similar growth potential were used in Exp. 1. Suckling behavior of calves was observed for two 24-h periods at three stages of lactation (average of 52, 104 and 167 d postpartum). Suckling frequency (suckling bouts/24 h) declined as milk production increased at 52 d of lactation (-.00382 bouts/kg milk) but was unrelated to milk production at later stages. Duration of suckling (minutes/suckling bout) increased with estimated level of milk production at all stages of lactation (means = .001556 min/kg milk). Total time suckling tended to increase as estimated level of milk production decreased at 52 d of lactation, but this component of suckling behavior was unaffected by milk level at later stages. Suckling frequency declined from 8.6 bouts/24 h at 52 d of lactation to 4.5 bouts/24 h at 167 d of lactation when averaged across all cows. Total minutes nursed/24 h declined in a similar manner (64 min/24 h to 44 min/24 h) between 52 and 167 d of lactation. Duration of each suckling bout did not change with stage. In the second experiment the relationship of suckling behavior to estimated milk production was evaluated at four early stages (average of 17, 38, 59 and 80 d postpartum) of lactation using 20 mature cows.(ABSTRACT TRUNCATED AT 250 WORDS)

Feedback of 17 beta-estradiol on secretion of luteinizing hormone during different seasons of the year.

The working hypothesis was that the amount of increase in secretion of luteinizing hormone (LH) that results from positive feedback of 17 beta-estradiol (E2) is dependent on season of the year in mature bovine females. Seven beef cows, ovariectomized approximately 2 mo before the initiation of the experiment, were used in the initial year (1983) of the study. Three of the ovariectomized cows (OVX-E2) received an sc E2 implant, which provided low circulating levels of E2. The remaining four cows (OVX) were not implanted. Blood samples were collected serially (at 10-min intervals for 6 h) at each spring and fall equinox and at each summer and winter solstice. This protocol was replicated with a different group of cows in 1985 (OVX-E2, n = 4; OVX, n = 6). Concentration of LH in blood serum was quantified in all samples. Concentration of E2 in blood serum was measured in pools of samples from each serial blood collection. Concentrations of E2 were higher (P less than .05) in the implanted cows. Mean concentration of LH and amplitude of pulses of LH were higher (P less than .05) at each season of the year in cows that were ovariectomized and implanted with E2 than in cows that were ovariectomized and did not receive E2. An effect of season of the year on mean concentration of LH was detected (P less than .01). No influence of season or E2 was detected for frequency of pulses of LH. There was no significant treatment X season interaction.(ABSTRACT TRUNCATED AT 250 WORDS)

Genetic selection for lifetime reproductive performance.

Genetic improvement of sow lifetime reproductive performance has value from both the economic perspectives of pork producers and the pork industry, but also from the perspective of ethical and animal welfare concerns by the general public. Genetic potential for piglets produced from individual litters is a primary determinant of lifetime prolificacy, but females must be able to sustain productivity without injury or death beyond the achievement of positive net present value. Evidence exists for between- and within-line genetic variation in sow lifetime performance, suggesting that improvements may be made by both line choices and genetic selection within lines. However, some of the same barriers to accurate within-line selection that apply to individual litter traits also present challenges to genetic selection for sow lifetime prolificacy: generally low heritabilites, sex-limited expression, expression after the age that animals are typically selected, and unfavorable genetic correlations with other traits in the profit function. In addition, there is an inherent conflict within the genetic nucleus herds where selections take place between the goal of shortened generation interval to accelerate genetic progress and the expression of sow lifetime traits. A proliferation in the industry of commercial multipliers with direct genetic ties and routine record flows to genetic nucleus herds provides a framework for accurate estimates of relevant genetic variances and covariances, and estimation of breeding values for sow lifetime traits that can be used in genetic selection.

Embryonic loss in sows with repeated propensity for small litter size.

Information is lacking as to the timing and cause of sows that repeatedly have low litter size over several parities. Sows evaluated for the present study had at least two parities either small or=12 (NL) litter size. Following breeding of sows with contemporary boars, reproductive tracts were obtained on day 30 of gestation. There was no difference (p > 0.10) between SL and NL sows in the number of CL, embryo weight or placental length. The total number of embryos and embryonic survival tended to be lower (p < 0.10) in SL sows compared with NL sows, but there were 5.1 less viable embryos (p < 0.03) in SL. Results indicate that time of conceptus loss in SL sows was variable throughout gestation.

Polymerase chain reaction-based polymorphisms in the porcine cholecystokinin (CCK) gene and assignment to chromosome 13.

Polymorphisms were identified in the porcine cholecystokinin (CCK) gene by digestion of products from polymerase chain reaction (PCR) with the restriction enzyme DpnII. Individuals from the European pig gene mapping project (PiGMaP) consortium reference families (eight full-sib families, 91 total progeny) were genotype to determine linkage relationships between the CCK gene and previously mapped loci. Linkage analysis revealed that the CCK gene is located on porcine chromosome 13.