Experimental maduromycosis I. Infection of mice with Phialophora jeanselmei

Infection with pure culture ofPhialophora jeanselmei was achieved in cortisone-treated mice but not in the untreated group. The peritoneal and subcutaneous lesions 2 to 5 mm. in diameter and 1 to 5 in number, were studied at intervals from 30 days to 85 days by routine histological and histochemical methods and confirmed by culture. The late (85 day) lesions were different from the initial (30 day) lesions in such a manner as to suggest the onset of hypersensitivity at some point of time after 30 days. The suggestive features present in the late and conspicuously absent in the early lesions were (a) marked leucocytic infiltration (b) massive necrosis (c) formation of grains by confluence of several necrotic microcolonies (d) fibroblastic proliferation. These findings are of interest to the understanding of clinical mycetoma since the hypersensitivity herein postulated might explain (a) the pathogenesis of human mycetoma (b) the morphogenesis of the grains so characteristic of the human lesion. Specific hypersensitivity is yet to be demonstrated and further experiments are in progress.     

Experimental transmission of human hepatitis delta virus to the laboratory mouse.

Human hepatitis delta virus (HDV), obtained from the serum of an experimentally infected woodchuck, was injected into either the peritoneal cavity or the tail vein of both adult CB17 mice and mice with a severe combined immunodeficiency (CB17-scid mice). Three lines of evidence indicated that the virus was able to reach the liver and infect hepatocytes: (i) the amount of HDV genomic RNA detected in the liver by Northern (RNA) analysis increased during the first 5 to 10 days postinoculation, reaching a peak that was about threefold the amount in the original inoculum; (ii) also detected in the liver was the viral antigenomic RNA, which is complementary to the genomic RNA found in virions, and is diagnostic for virus replication; and (iii) by immunoperoxidase staining of liver sections, the delta antigen was detected in the nuclei of scattered cells identifiable as hepatocytes. In all of the mice, clearance of the infection occurred between 10 and 20 days after inoculation. The half-life for clearance was about 3 days in CB17-scid mice, indicating that clearance of infection did not involve a T- and B-cell-dependent immune response. Cell-to-cell spread of the initial infection was not detected. One possible interpretation of our results is that HDV infection of hepatocytes is directly cytopathic. Also, the results imply that chronic infection of the liver in humans may require continuous spread of virus within the liver. Alternatively, HDV in the absence of helper virus may be unable to cause a chronic infection of hepatocytes in vivo.     

Growth of the laboratory mouse

Summary Body weights and tail lengths were observed every 3 days from birth to 60 days of age and every 6 days from 60 to 96 days in four lines of mice: C57BL/6J, an inbred; J, a synthetic outbred; GR, Goodale large body size line; and FR, Falconer large body size line. Mean 96-day body weights for lines C57BL, J, GR and FR were 25.4, 29.7, 48.8 and 49.1 gm for males, and 19.9, 23.8, 38.5 and 38.2 gm for females, respectively. Lines GR and FR gave identical body weights at all ages studied. Both of these lines had previously plateaued in response to selection for large body size. The variability in body weight was smallest for lines C57BL and J, intermediate for FR and highest for GR. The pattern of variance over time was very similar in all lines and both sexes, showing a minimum at birth and a maximum at age of inflection. Growth in tail length of the four lines showed similar between line differences except that length in GR was greater than in FR. Age at vaginal opening in females coincided closely with age of inflection in body weight growth. Age at point of inflection did not differ between lines but appeared to occur somewhat earlier in females than in males.

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Zusammenfassung Vier Linien von Laboratoriumsmäusen: der Inzuchtstamm C57BL/6J, der Kreuzungsstamm J, eine vonGoodale auf Körpergröße selektierte Linie GR und die vonFalconer auf Körpergröße ausgelesene Linie FR, wurden auf Körpergewicht und Schwanzlänge untersucht, und zwar von der Geburt bis zum 60. Lebenstage in 3 tägigem Abstand, von 60. bis 96. Lebenstage in 6tägigem Abstand. Am 96. Lebenstag betrugen die Durchschnittsgewichte für die 4 Linien 25,4; 29,7; 48,8 und 49,1 g für Männchen und 19,9; 23,8; 38,5 und 38,2 g für Weibchen. Die Linien GR und FR zeigten in allen untersuchten Altersstadien gleiche Gewichte. Beide waren durch vorangegangene Selektion auf Körpergröße weitgehend angeglichen. Die Variabilität des Gewichtes erwies sich bei den Linien C57BL und J als am geringsten, als intermediär bei FR und als am höchsten bei GR. Das Varianzmuster war bei allen Linien und für beide Geschlechter innerhalb des Untersuchungszeitraumes sehr ähnlich, mit einem Minimum bei der Geburt und einem Maximum am Ende der Wachstumsperiode (Inflexion). Das Schwanzwachstum zeigte die Linienunterschiede in gleicher Weise, lediglich der Stamm GR hatte eine größere Länge als FR. Das Öffnen der Vagina fällt zeitlich mit der Inflexion der weiblichen Tiere zusammen. Der Zeitpunkt der Inflexion differiert nicht zwischen den untersuchten Linien, scheint jedoch bei den weiblichen Tieren etwas früher als bei den männlichen zu liegen.

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Department of Animal Science.     

Cloning the laboratory mouse.

A brief account is given of early attempts to clone mammals (mice) by transferring cells (nuclei) of preimplantation embryos into enucleated oocytes, zygotes or blastomeres of two–cell embryos. This is followed by a brief review of recent successes using adult somatic cells: mammary gland cells for sheep, muscle cells for cattle and cumulus cells for mice. We have developed a technique for cloning the laboratory mouse by transferring cumulus cell nuclei into enucleated oocytes. With this technique, we have produced a population of over 80 cloned animals, and have carried the process over four generations. Development and fertility of these appear normal. However, the yield is very low; only approximately 1*b/ of injected oocytes are carried to term. The challenge is now to understand the reason for this high loss. Is it a problem of technique, genomic reprogramming, somatic mutation, imprinting or incompatible cell cycle phases?     

Hereditary erythroblastic anaemia in the laboratory mouse

Hereditary erythroblastic anaemia was found in a homozygous mutant (hea/hea) of an inbred strain CFO, which originated from noninbred CF#1 mice from Carworth Inc. This newly-described anaemia is inherited as an autosomal recessive and is lethal at 15-25 days of age. Erythrocytes of anaemic mice show striking polychromasia, anisocytosis, and poikilocytosis. One of the most marked features of this anaemia is the presence of large numbers of nucleated cells, mainly orthochromatophilic erythroblasts and myeloid cells, in the circulation. They also include immature erythroid and myeloid cells. Many naked nuclei appear on smears from circulating blood of anaemic infants. Erythrocytes, haematocrit percentage, and haemoglobin content of older anaemic infants were only about 50% of those of the normal. Formation of erythroid, myeloid cells, and megakaryocytes in the bone marrow seems to be progressively affected by mutant alleles in the anaemic infants.     

Immunity to Trichuris muris in the laboratory mouse

Of all the laboratory models of intestinal nematode infection, Trichuris muris in the mouse is arguably the most powerful. This is largely due to the fact that the ability to expel this parasite is strain dependent. Thus, most mouse strains readily expel T. muris. However certain mouse strains, and indeed some individuals within particular mouse strains, are unable to mount a protective immune response and harbour long term chronic infections. This unique model thus presents an opportunity to examine the immune events underlying both resistance to infection and persistent infection within the same host species, and in some cases, the same host strain.     

Hexamitiasis in a laboratory mouse colony

An acute fatal disease occurred in a mouse colony at the authors' institution. The disease caused 50% mortality among weanling mice, and was characterized clinically by depression, rough hair coat, and distention of the abdomen. The most prominent gross lesions were watery fluid and gas in the small intestine. Numerous organisms identified as Hexamita muris were seen in direct smears of the intestinal fluid. Microscopic and electron microscopic examination revealed the same organisms in the intestinal crypts, within the mucosal epithelium, and in the lamina propria. Treatment with dimetridazole controlled the clinical disease but did not eliminate the infection.     

Growth requirements of some fungi causing maduromycosis

Three strains ofMadurella mycetomi, two ofM. grisea, and two ofRhinocladiella mansonii have been studied for possible differences in growth requirements which might be used for distinguishing these species. Under the experimental conditions, an incubation temperature of 37C suitedM. mycetomi about as well as 30C.R. mansonii grew less well at 37C than at 30C, andM. grisea did not grow at the higher temperature. M. grisea andR. mansonii further differed fromM. mycetomi in that they required thiamine for growth. The pH tolerance of all the strains was very wide. Asparagine and potassium nitrate were readily utilized by all the strains, but ammonium salts were not. Urea was poorly used byM. mycetomi; the other species did not use it. A possible relationship ofM. grisea andR. mansonii is discussed.     

Comparisons of measures of dominance in the laboratory mouse

Dominance in groups of three male mice was assessed in the following ways: the observation of attack and submissive behaviours, the counting of tail wounds, competitive access to water after deprivation, tube dominance, territorial aggression, and access to female mice. Those mice assessed as dominant following behavioural observation had fewer tail wounds, fought more in the territorial aggression test and showed more interest in sexually receptive females. However, correlations of the measures (and subsequent factor analysis) produced no evidence of an underlying dimension which could be labelled dominance.     

An imputed genotype resource for the laboratory mouse

We have created a high-density SNP resource encompassing 7.87 million polymorphic loci across 49 inbred mouse strains of the laboratory mouse by combining data available from public databases and training a hidden Markov model to impute missing genotypes in the combined data. The strong linkage disequilibrium found in dense sets of SNP markers in the laboratory mouse provides the basis for accurate imputation. Using genotypes from eight independent SNP resources, we empirically validated the quality of the imputed genotypes and demonstrated that they are highly reliable for most inbred strains. The imputed SNP resource will be useful for studies of natural variation and complex traits. It will facilitate association study designs by providing high-density SNP genotypes for large numbers of mouse strains. We anticipate that this resource will continue to evolve as new genotype data become available for laboratory mouse strains. The data are available for bulk download or query at /. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

A genomewide functional network for the laboratory mouse

Establishing a functional network is invaluable to our understanding of gene function, pathways, and systems-level properties of an organism and can be a powerful resource in directing targeted experiments. In this study, we present a functional network for the laboratory mouse based on a Bayesian integration of diverse genetic and functional genomic data. The resulting network includes probabilistic functional linkages among 20,581 protein-coding genes. We show that this network can accurately predict novel functional assignments and network components and present experimental evidence for predictions related to Nanog homeobox (Nanog), a critical gene in mouse embryonic stem cell pluripotency. An analysis of the global topology of the mouse functional network reveals multiple biologically relevant systems-level features of the mouse proteome. Specifically, we identify the clustering coefficient as a critical characteristic of central modulators that affect diverse pathways as well as genes associated with different phenotype traits and diseases. In addition, a cross-species comparison of functional interactomes on a genomic scale revealed distinct functional characteristics of conserved neighborhoods as compared to subnetworks specific to higher organisms. Thus, our global functional network for the laboratory mouse provides the community with a key resource for discovering protein functions and novel pathway components as well as a tool for exploring systems-level topological and evolutionary features of cellular interactomes. To facilitate exploration of this network by the biomedical research community, we illustrate its application in function and disease gene discovery through an interactive, Web-based, publicly available interface at http://mouseNET.princeton.edu.