实验小鼠种群管理（英文）

2009年11月份在西安举行由中国实验动物学会发起的实验动物医药技术培训研讨会上,本人做了关于实验小鼠种群管理的演讲。其主题涵盖了小鼠繁殖性能的维护和基因工程种群的管理。本篇文章的目的在于强调其所涵盖的材料并为进一步研究提供参考。如若对本文所讨论的内容希望有更深刻的理解,这篇文章所引用的参考资料值得进一步的阅读。另外本文未涉及远交系小鼠的繁殖培育和基因管理,但如有需要可以联系本文作者,可推荐需阅读的材料清单。     

Granuloma formation to Capillaria hepatica eggs. I. Descriptive definition

The course of the cellular response in the liver to nonembryonated Capillaria hepatica (Bancroft, 1893) eggs given by intravenous injection into the portal circulation of unsensitized and sensitized mice was studied qualitatively and quantitatively. A gradual infiltration of predominantly mononuclear cells occurred around the eggs in the liver, leading to the formation of distinct granulomatous lesions characterized by macrophages and lymphocytes. This was followed by an infiltration of eosinophils. Previous intraperitoneal sensitization led to an earlier and an enhanced reaction to an intravenous challenge with eggs. Specificity of the cellular response was suggested by the lack of an enhanced reaction to presensitization with eggs of a closely related species, Trichuris muris. These studies indicate that granuloma formation to C. hepatica eggs has an immunological basis and furthermore the cell composition of the granuloma would suggest that a cell-mediated component may be involved as part of the specific response.     

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.     

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     

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     

Effects of traces of rare earth elements on the protozoanBlepherisma and on mice

The growth of the protozoanBlepherisma is stimulated by Lanthanum (La) at concentrations as low as 0.32 ppm. In mice Yttrium (Y) and Ytterbium (Yb) are absorbed, accumulated, and metabolized. Both rare earth elements (RE) exhibit a high affinity for teeth and bones, accumulation occurs and metabolism is slow. In the livers of RE-exposed mice, concentrations are variable. The liver is apparently capable of absorbing and discharging RE in a manner depending on metabolic activity. The main route of discharge for ingested REs is the alimentary canal. Exposure of pregnant mice to RE leads to rapid placental transfer of RE; 14.1% of the total amount of RE administered was detected in newborn mice. Young, developing organisms appear to be especially susceptible to RE accumulation.     

Transgenic markers for mammalian chimeras

Summary We describe the construction of aggregation chimeras between normal and transgenic embryos containing multiple copies of mouse -globin genes. The transgenic component of the chimeras is then detected in tissue sections by a DNA-DNA in situ hybridization technique, using a biotinylated DNA -globin probe and an avidin-linked alkaline phosphatase detection system. The general advantages of transgenic markers for chimeras are discussed.     

Ultrastructural study of a cytoplasmic bridge connecting a pair of erythroblasts in mice

Summary A unique cytoplasmic connection between erythroblasts was studied by electron microscopy in mouse hemopoietic tissues (fetal liver, fetal and neonatal spleen and adult bone marrow). Many pairs of interphase erythroblasts were connected by a cytoplasmic bridge that was very thin and sometimes long in comparison with telophase bridges. The stage of maturation of the cells in a pair was similar. Small numbers of microtubules ran along the cytoplasmic bridge; a mid-body was not seen. The plasma membrane at approximately the middle of the bridge bulged to form a ring-shaped ridge filled with dense amorphous substances; this was called a bulging ring. Thus, the cytoplasmic bridge between erythroblasts did not morphologically correspond to the telophase bridge in the usual cytokinesis. Cytoplasmic bridges were observed in various differentiating stages of erythroblasts, whereas other cell types of the hemopoietic lineage did not have such a bridge. The cytoplasmic bridge is unique to erythroblasts and provides an evidence for the atypical cytokinesis of the erythroblastic lineage.     

Release of Monoamines from Striatum of Rat and Mouse Evoked by Local Application of Potassium: Evaluation of a New In Vivo Electrochemical Technique

Local application of K+ via micropressure-ejection, coupled with in vivo electrochemical detection, was used to study stimulated release from monoaminergic nerve terminals in the striatum of anesthetized rats and mice. K+-evoked releases were reversible, reproducible, and dose-dependent. In contrast, releases of electroactive species could not be evoked by local ejection of Na+. The magnitudes and time courses of K+-evoked releases recorded from the caudate nucleus of mice were greater than those seen in rats. Local application of nomifensine, a putative catecholamine reuptake blocker, augmented the magnitudes and time courses of K+-evoked releases. Releases were also recorded from brain regions adjacent the striatum; these signals were always smaller than those seen in the caudate nucleus and had amplitudes that showed good correspondence to the relative degree of dopaminergic input to these areas. These data, taken together with other information in the literature, suggest that this new technique is well suited for in situ studies of monoamine release and reuptake in intact animals.     

Gastrocnemius Muscle Lipids in Relation to Diet in Two Mouse Mutants, 129Re-dy and A2G-adr, with Abnormal Muscle Function

The lipids of gastrocnemius muscle from normal and dystrophic (dy) mice of the Bar Harbor, 129Re strain were studied. Animals were fed diets containing either 3.1% or 1.1% of total calories as linoleic acid. Lipid analyses were also done on muscle from a new mouse mutant, A2G-adr, which has abnormal muscle function, characterised by an arrested development of the righting response. These animals were fed the "high" linoleic acid diet only. Total lipid, triacylglycerol, and cholesterol were elevated in the 129Re-dy irrespective of the diet, whereas A2G-adr possessed significantly higher levels of cholesterol. Total phosphorus (micrograms P/g muscle) and cholesterol/phospholipid ratios were elevated in the dy strains only. Cardiolipin was raised in the dy ("low" linoleic diet) and adr muscle, whereas phosphatidylcholine was lower in the adr strain only. Linoleic acid esterified to phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine was elevated whereas arachidonic acid in phosphatidylserine was decreased in both mutants. Docosahexanoic acid (22:6) in all three dy phospholipids was decreased, independent of dietary treatment. The adr strain possessed normal levels of this fatty acid. The results specifically point to an abnormality in long-chain polyunsaturated fatty acid metabolism in gastrocnemius muscle in the 129Re-dy mutant; in the adr mutant they could reflect an abnormal increase in the number of muscle mitochondria.