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SummaryEffects of a recessive gene causing high growth (hg) were studied on two major components of the growth axis in mice. Plasma and pituitary levels of growth hormone and plasma levels of insulin-like growth factor I (IGF-I) were measured in three lines homozygous forhg, each compared with a control line of alike genetic background but wild type for thehglocus (Hg). Line Gh (hghg) and line GH (HgHg) are from a line which had undergone long-term selection for high postweaning weight gain; line Ch (hghg) and line CH (HgHg) were extracted from the second backcross of Gh to C57BL/6J; line L54 (hghg) was from the sixth backcross to C57BL/6J (B6) (HgHg). Pituitary GH levels and plasma IGF-I levels were measured in both sexes at 3, 4·5, 6 and 9 wk of age. Plasma growth hormone was measured in 8- to 12-wk-old males at hourly intervals from 08.00 to 17.00. Body weight in lines homozygous forhgat 6 and 9 wk of age was 10–30% greater than in control lines. The ontogeny of this increased growth depended on genetic background. Pituitary growth hormone content was 52% lower in the twohghglines measured (lines Ch and Gh) than in control lines at 4·5, 6 and 9 wk. Plasma growth hormone levels were also much lower inhgmice, with values only 20–30% of those in their respective controls,hglines showed consistently low plasma growth hormone levels throughout the 9 hr sampling period, while control lines expressed the characteristic pulsatile hormone secretion. In contrast, plasma IGF-I levels were greater in line Ch (hghg) than in line CH (HgHg) at 3, 4·5 and 9 wk, and were also greater in line Gh (hghg)vs. line GH (HgHg) at 6 wk of age. The results suggest that the growth enhancing effect of thehggene occurs through an IGF-I-mediated process. In addition, the genetic background itself is also a factor in the phenotypic expression of the gene.

SUMMARYMice gaining 3 or more standard deviations above the mean were noted beginning in generation 25 in a line selected for high 21–42 day weight gain. The exceptional growth rate appears to be due to an autosomal recessive gene, based on the following: (1) the exceptional individuals appeared suddenly, in only one of 2 closely related sublines; (2) mating high growth individuals to unrelated, normal size strains produces relatively uniform F1's with mean gains below the mid-parent average; (3) F2's have a distribution markedly skewed towards high gain and a coefficient of variation approximately double that of F1's; (4) true breeding high growth strains can be established in one generation by intermating the largest F2's; (5) intermating normal F2's produces progenies with a distribution similar to the F1except for a few large segregates; (6) high growth segregates have been obtained in F2's from each of 4 successive backcrosses to the C57BL/6 inbred line. The symbolhg(high growth) is proposed for the postulated gene, which appears to be completely recessive. Frequency of positively identified segregates in F2's and backcrosses is on average less than 25 and 50%, due probably to some overlap ofHg- andhghgdistributions. Gain ofhghgindividuals from 21–42 days is 30–50% higher than ofHg- contemporaries; mature weight is also much higher, while 21-day weight ofhghgindividuals in segregating litters is slightly lower. Fertility of homozygotes ranges from normal to as much as 40% lower than for comparableHg- mice;hghgmice are not obese. The gene may provide a useful model for study of regulation of mammalian growth.

Summary. Selection for litter size (Line SI) and for post-weaning body weight gain (Line G) increased spontaneous ovulation rate in mature females by 69 and 73%, respectively, over that of randomly bred control mice (Line C). Inbreeding from S1 mice with selection for litter size produced highly inbred lines with elevated ovulation rates. Inbreeding from Line C mice produced a 21% divergence among lines, but did not depress the mean ovulation rate. Crosses of these lines revealed little heterosis in ovulation rate. LH receptors were induced by treating females from 22 days of age with diethylstilboestrol for 4 days and FSH for 2 days. The in-vitro binding of 1 25I-labelled hCG per \g=m\gDNA decreased 56% in response to selection for litter size and increased 57% in response to selection for body weight gain, indicating high susceptibility of this trait to genetic change. Inbreeding from Line C mice produced a 135% divergence amongst lines, but did not depress the mean LH receptor induction. Body weight had significant effects on ovulation rate and LH receptor induction. These results show that selection for litter size and for rapid post-weaning body weight gain increases ovulation rate, but we suggest that different mechanisms are involved in these responses.

Pregnant (N = 10) and non-pregnant (N = 10) ewes were bled every 2 h from Days 12 to 17 after oestrus (oestrus = Day 0). Plasma concentrations of progesterone, 15-keto-13,14-dihydro-PGF-2 alpha and 11-ketotetranor-PGF metabolites were determined in all samples. The number of PGF-2 alpha pulses in non-pregnant ewes was 8.2 +/- 0.4 (mean +/- s.e.m.) with an interpulse interval of 10.7 +/- 0.7 h. Two or 3 pulses of low frequency (interpulse interval = 13.4 +/- 1.6 h) occurred in most non-pregnant ewes before the onset of luteolysis; the interpulse interval then decreased to 7.9 +/- 0.4 h for the 6.0 +/- 0.3 pulses temporally associated with luteolysis. In contrast, the number of PGF-2 alpha pulses in pregnant ewes was lower (2.5 +/- 0.7, 0-8) and the interpulse intervals longer (18.9 +/- 6.1 h). Most pulses occurred on Days 14 and 15 in the pregnant and non-pregnant ewes. The mean concentrations of both PGF-2 alpha metabolites in non-pregnant ewes were highest on Day 15 while basal levels of both metabolites remained constant at all times. In pregnant ewes, the mean concentrations of both metabolites were highest on Day 14; basal concentrations of both metabolites were also highest on Day 14. The mean concentrations of 15-keto-13,14-dihydro-PGF-2 alpha were higher in pregnant than in non-pregnant ewes on Days 13 and 14 (P less than 0.05) and higher in non-pregnant than pregnant ewes on Day 15 (P less than 0.05). The basal concentrations of the 15-keto metabolite were higher in pregnant than non-pregnant ewes at Days 13, 14, 15, 16 and 17 (P less than 0.05). Both the mean and the basal concentrations of 11-ketotetranor-PGF metabolites were higher in pregnant than in non-pregnant ewes on Day 14 (P less than 0.05). It is concluded that uterine production of PGF-2 alpha peaks at Days 14-15 after oestrus in pregnant and non-pregnant ewes. Patterns of release differ, however, in that non-pregnant ewes have a pulsatile PGF-2 alpha pattern superimposed on a constant baseline, while pregnant ewes have an increasing basal secretory pattern which is more nearly continuous, i.e. not pulsatile in form. Modification of pulsatile PGF-2 alpha synthesis and release is therefore a key aspect of prolongation of luteal function at the beginning of pregnancy in the ewe.

Mating initiates a pattern of prolactin secretion composed of daily surges which appear with semicircadian rhymicity until Day 8 (Day 0 = Day of plug detection) of mouse gestation. On Day 8, the diurnal (1500-2100 h) prolactin increase diminishes in magnitude in a line selected for high embryo survival (E). By Day 9, the diurnal surge has been terminated. The nocturnal prolactin surge (2400-0900 h) is present in the line E through Day 9 of pregnancy, but on Day 10 it disappears. The temporal pattern of prolactin secretion in a randomly bred control line (C) is similar on Days 2 and 4 of pregnancy to that observed in line E. Collection of head blood and/or trunk blood had no effect on plasma prolactin concentration in either line C or E if no more than 30 seconds elapsed between cage handling and sample collection. In contrast, prolactin levels were dramatically elevated in the blood of animals placed in the same room in which serial exsanguination was performed.

Male reproductive capacity was examined in 5 lines of mice which differed markedly in mature body weight (30-73 g) due to selection for growth and/or substitution of the high growth gene (hg). Testes weight ranged from 0.75-0.77% of body weight in control lines to 0.33% in the largest mice which had the hg gene in a growth selected background. Both selection for growth and the hg gene in a control background reduced absolute testes size (0.200 and 0.207 g vs 0.236 and 0.228 g in control lines) as well as relative testes size although body weight was increased by at least 50%. Although the combination of growth background and hg gene reduced sperm production per g testis compared to the outbred control, the primary cause of reduced sperm production per mouse in lines containing either the growth background or the hg gene alone was reduced absolute testes size. At 24, but not at 11, weeks of age, the hg gene reduced sperm motility. In these lines, high genetic potential for post-weaning growth was associated with decreased male reproductive capacity.

Milk records of up to the first three lactations of artificially sired Holstein daughters and their dams were used to estimate heritability from both daughter-dam regression and paternal half-sib correlation. The within-herd estimates from records expressed as deviations from herd-mate averages were .37, .30, and .24 from daughter-dam regression for the first three lactations; and the corresponding estimates from halfsib correlation were .24, .21, and .23. These results suggest a large maternal effect in the first lactation, a small amount in the second, and little in the third lactation. Analysis of the records not as deviations gave the same pattern for the daughter-dam regressions, but confounding of sires with year-seasons apparently biased the half-sib correlations upward. The consequences of considering unequal heritability for different lactations if the apparent difference is due to maternal effects is illustrated for selection for first-lactation breeding value from up to three records on the cow herself and on her dam.

The squeeze machine method as evaluated for use on California and Texas wools, while not as accurate as the side sample method, is much easier, quicker, and less expensive. The animals can be rated in order of clean wool production more accurately than by grease weight, for high-shrinking wools. Rating of animals in this manner allows the breeder to choose those of higher productivity. The side sample method in most cases cannot be used by untrained personnel while the squeeze machine can. In high rainfall areas and with breeding stock producing high-yielding fleeces, grease fleece weight may equal or surpass the squeeze machine in accuracy. The machine does not appear to be of sufficient accuracy to determine shrinkage of wools for sales purposes.

EVERAL investigators have reported the results of selecting for measures of growth rate or body size in mice (GOODALE 1938; MACARTHUR 1944, 1949; FALCONER 1953; RAHNEFELD et al. 1963; ROBERTS 1967). Direct response to selection has been substantial in each of these cases. Litter size has been shown to increase in several of the lines, the increase in the experiment reported by RAHNEFELD et al. (1966) being nearly three mice per litter. This suggested the possibility that litter size might be increased more rapidly by indirect selection, for body weight gain, than by direct selection, particularly since results of selection for litter size have indicated quite low heritability for this trait (FALCONER 1960; DALTON and BYWATER 1963). A line selected for rapid post-weaning gain was therefore included in an experiment in which the effects of selecting for litter size and its components were being studied. This permitted a direct comparison of the effects of these two kinds of selection, using the same base population and selecting contemporarily within the same laboratory. Results from this project of selecting for litter size and for its components have been reported (BRADFORD 1968, 1969). The present paper reports the direct and correlated responses to selection in the rapid gain line and lines derived from it. The results suggest a complex relationship between body size and reproduction in the mouse, and provide additional evidence on the nature of the genetic control of litter size. MATERIALS AND METHODS The base population was a cross of four inbred lines (C57BL/6JJ, AKR/J, C3H/J, DBA/2J). Details of the formation of the stock and of the management of the colony are given in an earlier paper (BRADFORD 1968). The diet used was commercially prepared “White Diet” with specified minimum protein and fat contents of 24% and 7% respectively. The strain selected for rapid post-weaning gain was designated line G. Eighteen males were each mated to two females each generation. Litters were counted the day of birth, and sexed at two days of age when litters of more than 10 were reduced to 10; there was no augmentation of litters with fewer than 10. Young were weaned, weighed, and ear notched at 21 days and caged, by sex, 4 to 7 per cage to 42 days of age when they were reweighed. Those individuals with the greatest weight increase between the two weighings were selected, regardless of litter, litter size or coat color genotype. Normally more than the necessary 18 males and 36 females were kept at six weeks, but only those numbers were mated except in the latest generations when numbers were increased slightly. Matings were made at approximately nine weeks of age, thus producing four generations per year. Males remained with the females for 7-10 days in the early part of

Concentrations of plasma LH and FSH were measured by radioimmunoassay in four strains of mice maintained in controlled lighting. Gonadotrophin levels in an unselected control line (Line C) were measured under the following conditions: induced cycles; spontaneous cycles; cycles in absence of males and post-partum cycles. In mice with induced cycles, LH reached a mean of about 40 ng/ml between 16.00 and 17.00 hours of pro-oestrus. Levels of FSH reached a peak of around 2800 ng/ml about 2 hr later, between 19.00 and 20.00 hours, suggesting that the function of FSH is to stimulate growth of the crop of follicles which will ovulate during the succeeding oestrous cycle. Spontaneously cycling mice ofLine C also had a mean LH concentration of about 40 ng/ml, but this peak began 1 hr later at 17.00 hours of pro\x=req-\ oestrus and persisted for about 4 hr. No well-defined FSH peak was found. Only two ofseventy individually caged females killed during pro\x=req-\ oestrus had LH or FSH levels greater than the mean di-oestrous levels in induced and spontaneously cycling animals. Within 24 hr of parturition, there was no one time when the majority of mice showed elevated levels of LH or FSH. The timing and magnitude of gonadotrophin release during pro-oestrus of induced cycles in lines successfully selected for small litter size, high embryo survival, and high ovulation rate were the same as for Line C, suggesting that the principal effect of selection was probably to alter the sensitivity of the target organs.

A strain of mice (S1) was successfully selected for large litter size for 31 generations, increasing the mean by 4.2 young per litter. After generation 31, there was no further progress and it was concluded that a selection plateau had been reached. Realized heritability decreased during the course of the experiment from 0.16 ± 0.06 for the first 15 generations to 0.00 ± 0.03 for generations 30 through 45. — In order to explore the nature of the selection plateau, the following groups were derived from line S1 at generation 34 or 35: Upward selection with inbreeding (SF), random (relaxed) selection (SO), and downward selection (SR). Selections were carried out for 10 or 11 generations. The means of SO and SF were similar to those of S1, ruling out any major effect of natural selection or overdominance. SR decreased, the mean averaging 2.3 young per litter below that of S1 during the last three generations. The fact that SR responded to selection indicates that genetic variance was still present in the plateaued population. The SF sublines were crossed when the inbreeding was 95% and a new line, SX, was formed. SX was maintained for three generations and the difference of +0.7 young per litter above the contemporary generations of S1 was significant. The results from this experiment suggest that the selection plateau in line S1 was caused by reduction of additive genetic variance to a very low level. Some nonadditive genetic variance remained, however, and was attributed to recessive alleles at low frequency. In agreement with results reported by Falconer (1971), inbreeding with selection followed by crossing of the inbred sublines proved to be effective in overcoming a selection plateau in litter size.

Ewes (N = 32) were bled every 2 h from 5 days before expected oestrus until the end of oestrus. Plasma concentrations were determined for progesterone to monitor luteal activity and for the prostaglandin F-2 alpha (PGF-2 alpha) metabolites, 15-keto-13,14-dihydro-PGF-2 alpha and 11-ketotetranor-PGF to determine uterine synthesis and release of PGF-2 alpha. Most of the variation in cycle length was associated with the time of onset of luteolysis, the timing of events after luteolysis being constant and not related to cycle length. The time of occurrence of the first PGF-2 alpha pulse and the interval between this pulse and the start of luteolysis were the two main determinants responsible for oestrous cycle length. Several PGF-2 alpha pulses with interpulse intervals of 15.9 h occurred before the onset of functional luteolysis compared with 7.7 h for pulses associated with luteolysis. The numbers of PGF-2 alpha pulses and interpulse intervals were similar for oestrous cycles of different lengths. While a gradual decline in progesterone concentrations was observed before functional luteolysis in the ewes with longer cycles, this did not appear to be an integral part of the stimulus which initiates the pulse frequency of PGF-2 alpha required for luteolysis. We therefore suggest that differences in oestrous cycle length in the ewe are determined by the time of the onset of PGF-2 alpha pulsatile release, and especially by the time of increased pulse frequency.

Summary. Results of egg transfer and of reciprocal crossing among breeds of sheep with a range of 1 week in mean gestation period indicate that the genotype of the fetus is the major determinant of the duration of gestation, over a range of litter sizes from 1 to 5 and a wide range of combinations of size of donor and recipient breeds. It is concluded that the fetus accounts for at least two-thirds of the genetic variation in gestation period in this species. Evidence for the role of the fetus in determining the duration of gestation comes from two independent sources, namely endocrine studies of the fetal pituitary-adrenal axis (Liggins, Kennedy & Holm, 1967; Liggins, 1969), and genetic studies, with the most critical evidence provided by interbreed egg transfer (Dickinson, Hancock, Hovell, Taylor & Wiener, 1962; Moore, 1968). We present here the results of interbreed egg transfer and crossbreeding experiments involving breeds with a wider range of gestation periods than have been used in earlier experiments. They provide striking evidence of the role of the fetal genotype in determining the duration of gestation in this species. Descriptions of the animals involved in the egg transfer experiment and of the procedures used for synchronizing oestrus in donors and recipients have been reported by Bradford, Quirke & Hart (1971). The time of onset of oestrus was recorded twice daily, and the actual time of parturition was recorded to the nearest hour, except for ewes lambing unattended during the night for which parturition was listed as occurring at 07.00 hours. The duration of gestation was calculated to the nearest half day. Where donor and recipient ewes were not exactly synchronized, the time of onset of oestrus in the donor was used as the basis for computing the gestation period; all but seven of the fifty-three recipient ewes for which gestation periods are reported were synchronized within 12 hr of the donor. In addition to the pregnancies following egg transfer, data were obtained on seventy-seven control pregnancies, mostly of donor ewes, following intra-breed mating. The same rams, in most cases one or two per breed, were used at the oestrus from which eggs were collected and on the control group. Extensive data were also available on gestation periods from the parental flocks. Lambs in the experiment were born during a 3-month period, March to

Analysis of 60,000 pairs of daughter and dam first-lactation records expressed as deviations from herd-mate averages for five breeds yielded markedly different heritability estimates from daughter-dam regression than from paternal half-sib correlation. These results suggest that 18% of the within-herd variation is due to genetic maternal effects. The same records analyzed as mature equivalent records and not as deviations but by a sire by herd model did not show this difference. Confounding between year and sire effects probably biased the intra-class correlation estimates upward in the latter analysis, since year effects were not included in the statistical model.

AN association between lifespan and early growth rate as affected by nutritional manipulation has been reported; high intake–rapid growth apparently contribute to shorter lifespan, and low intake–slow growth to longer lifespan1,2. Genetically determined rapid growth has also been reported to be associated with shortened lifespan3.

An increase in mean prolificacy is a goal for many sheep production systems, but it is also desirable that variation be minimized around the optimum value. Lambs born in litters of 3 or 4 can be reared with intensive management, but at higher input costs than for twins. Thus for a mean litter size (LS) goal of 2.0, producers desire the maximum possible proportion of twins with as few singles and litters of 3 or more as possible. Coefficients of variation for ovulation rate (OR) range from about 22 % for Romanov to about 40 % for Booroola Merinos; breed CV’s for LS vary less. The most uniform LS’s are achieved by populations with a uniform OR and high prenatal survival. Variability in Booroola populations results in part from segregation of a gene with large effect on OR, but variation is high within genotypes (FF or F+). Among breeds where high prolificacy appears to be inherited quantitatively, there are differences in variability, with Romanov quite uniform, Finnsheep intermediate, and D’Man more variable. The possibility of a gene with large effect in the D’Man breed, in addition to many favorable quantitative genes for prolificacy, has not been ruled out. In general, these three breeds (and some others) transmit their prolificacy additively, making it possible to choose a wider range of mean prolificacy values by crossing and backcrossing with such breeds than by use of a major gene such as the Booroola. Data on variability of first and later generation crossbreds between non-prolific and different prolific breeds are now available.