Ascorbic acid synthesis and concentrations in organs of copper-deficient and brindled mice

Copper deficiency was studied in mice to investigate an interaction between copper and ascorbic acid. Twelve-day-old mutant brindled mice that exhibited signs of copper deficiency were compared to their normal brothers as well as to age-matched suckling mice that were copper deficient (-Cu) because their dams were consuming a copper-deficient diet throughout gestation and lactation, and a fourth group of copper-supplemented ( + Cu) suckling mice that served as dietary controls. Dietary copper deficiency was also produced in older mice by beginning the treatment at birth and continuing for 7 wk. Organ ascorbate levels were determined by high performance liquid chromatography with electrochemical detection. Differences caused by diet and genetics were evident but age-dependent. Compared to controls, liver and kidney ascorbate levels did not change remarkably in young or old copper-deficient mice. Cardiac ascorbate levels were higher in 7-wk-old - Cu mice and lower in 12-d-old - Cu mice, despite hypertrophy in both cases. Spleen ascorbate levels were lower in older -Cu mice and higher in 12-d-old mice, but total spleen ascorbate reflected the hypertrophic and atrophic size in the older and younger -Cu mice, respectively. Brindled mutants had an extremely low level of ascorbate in spleen. Plasma ascorbate was lower in 7-wk-old - Cu mice. Reasons for the alterations in ascorbate levels are not known. Synthesis in liver from D-glucuronate was not altered by dietary copper deficiency in 7-wk-old mice. Synthesis was lower in livers from 12-d-old - Cu and brindled mice compared to control values. However, the difference correlated better with body weight of the mice rather than with degree of copper deficiency. Consequences of the altered organ levels of ascorbate in copper-deficient mice are not completely known.     

Spermatogenesis is modified by food intake in mice

Spermatogenesis is generally viewed as being resistant to reduced food intake in inbred strains of adult mammals. This consensus stems from studies that have failed to place testicular responses within the context of a species' reproductive characteristics. We exposed two species of wild rodents, house mice and deer mice, to a mild but sustained food restriction (30% reduction of ad libitum consumption for 5 weeks). Reproductive adjustments made by each species to inanition were strikingly different. Food restriction failed to modify spermatogenesis in house mice, but evoked a continuum of testicular responses in deer mice ranging from normal spermatogenesis to azoospermia. These findings have several novel implications: 1) modest food restriction evokes species-specific adjustments in testicular function, and 2) intraspecific variation in spermatogenesis suggests robust individual differences in sensitivity to alterations in food intake. Taken together, our findings underscore the importance of considering the effects of food intake on male reproduction within the framework of a species' physiological and evolutionary background.     

Developmental variation in copper,zinc and metallothionein mRNA in brindled mutant and nutritionally copper deficient mice

The concentrations of copper, zinc and metallothionein-I (MT-I) mRNA were determined in the liver, kidney and brain of the brindled mutant mouse from birth until the time of death. Despite accumulation of copper in the kidney of the mutant, MT-I mRNA concentrations were normal. There was no difference between the MT-I mRNA in the brain of mutant and normal in the first 10 days of life, but after day 10 metallothionein mRNA levels were increased in the mutant. The concentration of copper was very low in the liver of the mutant, and on day 6 after birth the metallothionein mRNA was also reduced by about 50%. This reduction was not seen in copper-deficient 6-day-old pups, despite very low hepatic copper levels. This suggests that the lower hepatic MT-I mRNA in the day 6 brindled mouse was not simply due to the reduction in hepatic copper and also that hepatic copper is not regulating metallothionein gene expression the liver of neonatal mice. After day 12 hepatic MT-I mRNA levels were elevated in mutant and in copper deficient mice, both of which die at 14 to 16 days. These increases and the increase in brain MT-I mRNA in older mutant mice are likely to be caused by stress. Overall the results support the conclusions that the brindled mutation does not cause a constitutive activation of the metallothionein genes, and that the differences in metallothionein mRNA between mutant and normal are most probably secondary consequences of the mutation.     

Copper metabolism in mottled mouse mutants: distribution of 64Cu in brindled (Mobr) mice.

1. Duodenal injection of 64Cu in treated adult mutant mice (Mobr/y) revealed severe malabsorption of copper. In suckling mutants, malabsorption was less severe, owing to delayed absorption between 2 and 5 h after injection. Pinocytosis at the distal small intestine seems the likely explanation for this difference, and this is supported by results of ileal injection of radioisotope in the suckling mice. 2. The distribution of 64 Cu in various organs was measured in suckling normal, mutant and heterozygote mice and in adult normal and mutant mice during 48 h after intracardiac injection. Excessive accumulation of radioisotope was observed in most extrahepatic organs of mutant and heterozygote mice and was most pronounced in kidney. This could not be explained by initial copper deficiency. The livers of suckling mutant and heterozygote mice lost radioisotope rapidly after normal initial uptake. This pattern was not seen in adult mutants.     

Sex-linked inheritance in fronto-metaphyseal dysplasia

The author reports a family study of fronto-metaphyseal dysplasia in a 2 months-old child, in his mother and maternal grand-mother. The child is the more severely affected, while the mother and the grand-mother have less severe manifestations of the syndrome. This evidence permits to confirm the X-linked recessive inheritance of the disease, with severe manifestations in males and variable expression in female carriers.     

Position effect variegation in yeast

Classically, position effect variegation has been studied in Drosophila and results when a euchromatic gene is placed adjacent to either centromeric heterochromatin or to a telomeric domain. In such a circumstance expression of the locus variegates, being active in some cells and silent in others. Over the last few years a comparable phenomenon in yeast has been discovered. This system promises to tell us much about this curious behaviour. Indeed, experiments reported recently⁽¹⁾ indicate that the variegation of a yeast telomeric gene is cell-cycle regulated. The results suggest the following model. During DNA replication there is a disassembly of chromatin that allows a competition between silencing factors and trans-activators to take place. Thus, reassembly of the domain may result in either the repression or the expression of the affected gene and, hence, produce a variegating phenotype.     

On variegation in Primula sinensis

Ohne Zusammenfassung     

Developmental variation in copper, zinc and metallothionein mRNA in brindled mutant and nutritionally copper deficient mice.

The concentrations of copper, zinc and metallothionein-I (MT-I) mRNA were determined in the liver, kidney and brain of the brindled mutant mouse from birth until the time of death. Despite accumulation of copper in the kidney of the mutant, MT-I mRNA concentrations were normal. There was no difference between the MT-I mRNA in the brain of mutant and normal in the first 10 days of life, but after day 10 metallothionein mRNA levels were increased in the mutant. The concentration of copper was very low in the liver of the mutant, and on day 6 after birth the metallothionein mRNA was also reduced by about 50%. This reduction was not seen in copper-deficient 6-day-old pups, despite very low hepatic copper levels. This suggests that the lower hepatic MT-I mRNA in the day 6 brindled mouse was not simply due to the reduction in hepatic copper and also that hepatic copper is not regulating metallothionein gene expression the liver of neonatal mice. After day 12 hepatic MT-I mRNA levels were elevated in mutant and in copper deficient mice, both of which die at 14 to 16 days. These increases and the increase in brain MT-I mRNA in older mutant mice are likely to be caused by stress. Overall the results support the conclusions that the brindled mutation does not cause a constitutive activation of the metallothionein genes, and that the differences in metallothionein mRNA between mutant and normal are most probably secondary consequences of the mutation.     

Sex-linked genes in age-structured populations.

We study the progress towards equilibrium of the frequencies of sex-linked genes in elementary discrete time models of age-structured, overlapping generation populations. It is found that, if a finite upper age limit is assumed, the difference in the frequencies of an allele in males and females will oscillate as in the familiar non-overlapping generation models, although the oscillations may be irregular. Monotonic convergence of that difference, as found by Nagylaki (1975) in continuous-time overlapping generation models without age-structure, occurs in the models considered here only when there is no upper age limit and when there is "sufficient" overlap of generations.     

Sex-linked hybrid sterility in a butterfly

Recent studies, primarily in Drosophila, have greatly advanced our understanding of Haldane's rule, the tendency for hybrid sterility or inviability to affect primarily the heterogametic sex (Haldane 1922). Although dominance theory (Turelli and Orr 1995) has been proposed as a general explanation of Haldane's rule, this remains to be tested in female-heterogametic taxa, such as the Lepidoptera. Here we describe a novel example of Haldane's rule in Heliconius melpomene (Lepidoptera; Nymphalidae). Female F1 offspring are sterile when a male from French Guiana is crossed to a female from Panama, but fertile in the reciprocal cross. Male F1s are fertile in both directions. Similar female F1 sterility occurs in crosses between French Guiana and eastern Colombian populations. Backcrosses and linkage analysis show that sterility results from an interaction between gene(s) on the Z chromosome of the Guiana race with autosomal factors in the Panama genome. Large X (or Z) effects are commonly observed in Drosophila, but to our knowledge have not been previously demonstrated for hybrid sterility in Lepidoptera. Differences in the abundance of male versus female or Z-linked versus autosomal sterility factors cannot be ruled out in our crosses as causes of Haldane's rule. Nonetheless, the demonstration that recessive Z-linked loci cause hybrid sterility in a female heterogametic species supports the contention that dominance theory provides a general explanation of Haldane's rule (Turelli and Orr 2000).     

A comparison of phenotype and copper distribution in blotchy and brindled mutant mice and in nutritionally copper deficient controls

The murine mottled mutants brindled, Mo br, and blotchy, Mo blo, are valuable animal models for the study of mammalian copper metabolism. In this paper, we present data showing that a nutritionally copper deficient suckling mouse, Cu-, with strong phenotypic similarities to the brindled mutant can be produced by feeding genetically normal dams a copper deficient diet (0.1-0.4 ppm Cu2+) from the day of mating. Comparisons of copper distribution between the Cu- mice and brindled mutants indicate that when a small dose of copper (0.5-0.9 micrograms Cu2+) was administered by intracardiac injection, the copper was abnormally distributed, and that the pattern of tissue distribution was very similar in Cu- mice and brindled mutants 24 h after injection. When, however, a treatment dose (50 micrograms Cu2+) was injected subcutaneously, and tissues assayed 3 d after injection, copper distribution in Cu- mice and brindled mutants was clearly different. Copper deficiency in Cu- suckling mice is entirely derived from maternal effects. Evidence that maternal effects may also influence the survival and phenotype of the brindled and blotchy mutants was obtained by comparing the viability of mutants born to dams carrying mottled mutations on one or both X chromosomes.     

Performance of genomic selection in mice

Selection plans in plant and animal breeding are driven by genetic evaluation. Recent developments suggest using massive genetic marker information, known as "genomic selection." There is little evidence of its performance, though. We empirically compared three strategies for selection: (1) use of pedigree and phenotypic information, (2) use of genomewide markers and phenotypic information, and (3) the combination of both. We analyzed four traits from a heterogeneous mouse population (http://gscan.well.ox.ac.uk/), including 1884 individuals and 10,946 SNP markers. We used linear mixed models, using extensions of association analysis. Cross-validation techniques were used, providing assumption-free estimates of predictive ability. Sampling of validation and training data sets was carried out across and within families, which allows comparing across- and within-family information. Use of genomewide genetic markers increased predictive ability up to 0.22 across families and up to 0.03 within families. The latter is not statistically significant. These values are roughly comparable to increases of up to 0.57 (across family) and 0.14 (within family) in accuracy of prediction of genetic value. In this data set, within-family information was more accurate than across-family information, and populational linkage disequilibrium was not a completely accurate source of information for genetic evaluation. This fact questions some applications of genomic selection.     

A modified pedigree method of selection

Summary A dismal 81% failure of newly bulked lines against checks was observed in Indian wheat material evolved by the pedigree method. This is considered to be the consequence of selection in space planting in early generations followed by yield tests in a competitive environment which did not allow any scope of selection for competitive ability. Thus, most of the homozygous lines, which were until now raised and carried forward under space planting, failed to compete with the checks for yield in close planting. It is, therefore, necessary to modify the method to combine both the competitive ability and identity of selected plants. The proposed modified procedure involves raising the population under spaced planting as well as under drilling from F₂ onwards. Evaluation for tiller index marks an important step. On the basis of tiller index, single plants are isolated from spaced populations. Steps of the modified procedure are outlined in detail. The modified method, which economises on breeders' workload and other physical inputs, besides having other advantages, can also be used for certain other grain crops. Preliminary results based on the modified method during the past two seasons have indicated its utility.