Host age and genotypic effects on enterotropic mouse hepatitis virus infection

Intestinal lesions due to infection with an enterotropic strain of mouse hepatitis virus (MHV-Y) were found to be more severe and wide-spread in BALB/cByJ and Cr1:CD-1(ICR) mice than in SJL mice inoculated at 1 week of age, using nonparametric ranking analysis. Lesions and viral antigen were limited largely to the bowel, but also occurred in the liver and brain of some mice. BALB/cByJ mice developed a particularly high prevalence of brain infection, resulting in mortality after the enteric phase of infection had ceased. MHV-Y antigen was present in neurons, glia and vascular endothelium in a vascular distribution. Cr1:CD-1(ICR) pups inoculated with MHV-Y at 4 or 7 days of age developed severe typhlocolitis, enteritis and encephalitis with moderate mortality. Pups infected at 2 or 3 weeks of age had mild intestinal lesions with minimal alteration of mucosal architecture, no encephalitis and no mortality. These results demonstrate that host age and genotype influence the course of enterotropic mouse hepatitis virus, as has been shown previously with non-enterotropic, respiratory-type strains of mouse hepatitis virus.     

Nesidioblastosis associated with hyperglycemia in two squirrel monkeys (Saimiri sciureus)

Abstract: Nesidioblastosis associated with progressive weight loss and hyperglycemia was diagnosed in two mid-adult, wild-caught, male squirrel monkeys (Saimiri sciureus). Hyperglycemia, glucosuria, and abnormal glucose tolerance test results were found when the monkeys were presented for clinical evaluation for chronic weight loss, episodic dehydration, hypothermia, and lethargy. Immunohistochemical studies of the pancreatic tissue demonstrated that the proliferating endocrine cells stained predominantly glucagon-positive in the most severely affected monkey.     

The lepidopteran mitochondrial control region: structure and evolution

For several species of lepidoptera, most of the approximately 350-bp mitochondrial control-region sequences were determined. Six of these species are in one genus, Jalmenus; are closely related; and are believed to have undergone recent rapid speciation. Recent speciation was supported by the observation of low interspecific sequence divergence. Thus, no useful phylogeny could be constructed for the genus. Despite a surprising conservation of control-region length, there was little conservation of primary sequences either among the three lepidopteran genera or between lepidoptera and Drosophila. Analysis of secondary structure indicated only one possible feature in common--inferred stem loops with higher-than-random folding energies-- although the positions of the structures in different species were unrelated to regions of primary sequence similarity. We suggest that the conserved, short length of control regions is related to the observed lack of heteroplasmy in lepidopteran mitochondrial genomes. In addition, determination of flanking sequences for one Jalmenus species indicated (i) only weak support for the available model of insect 12S rRNA structure and (ii) that tRNA translocation is a frequent event in the evolution of insect mitochondrial genomes.      

Dietary, bacterial, and host genetic interactions in the pathogenesis of transmissible murine colonic hyperplasia

Transmissible murine colonic hyperplasia, cuased by a variant of Citrobacter freundii (4280). was shown to be modified by diet and by host strain and species. Four different diets fed to mice inoculated with C frundii 4280 were found to have a significant but varying influence on the severity of hyperplasia. Diet also influenced the colonic crypt height of uninoculated, control mice. F344 rats, Syrian hamsters, and NIH Swiss [N:(S)], C57BL/6J, C3H/HeJ, and DBA/2J mice were inoculated with C freundii 4280. Marked strain differences were noted in the mice in mortality and severity of the colonic hyperplasia. The NIH Swiss mice had the greatest and the C57BL/6J mice had the least mucosal hyperplasia. The rats and hamsters did not develop disease or maintain infection after inoculation with the organism. Twenty isolates of Citrobacter from a range of biologic sources were inoculated into susceptible mice, but only mice inoculated with C freundii 4280 developed the disease.     

Combined monte carlo and molecular dynamics simulation of fully hydrated dioleyl and palmitoyl-oleyl phosphatidylcholine lipid bilayers

We have applied a new equilibration procedure for the atomic level simulation of a hydrated lipid bilayer to hydrated bilayers of dioleyl-phosphatidylcholine (DOPC) and palmitoyl-oleyl phosphatidylcholine (POPC). The procedure consists of alternating molecular dynamics trajectory calculations in a constant surface tension and temperature ensemble with configurational bias Monte Carlo moves to different regions of the configuration space of the bilayer in a constant volume and temperature ensemble. The procedure is applied to bilayers of 128 molecules of POPC with 4628 water molecules, and 128 molecules of DOPC with 4825 water molecules. Progress toward equilibration is almost three times as fast in central processing unit (CPU) time compared with a purely molecular dynamics (MD) simulation. Equilibration is complete, as judged by the lack of energy drift in 200-ps runs of continuous MD. After the equilibrium state was reached, as determined by agreement between the simulation volume per lipid molecule with experiment, continuous MD was run in an ensemble in which the lateral area was restrained to fluctuate about a mean value and a pressure of 1 atm applied normal to the bilayer surface. Three separate continuous MD runs, 200 ps in duration each, separated by 10,000 CBMC steps, were carried out for each system. Properties of the systems were calculated and averaged over the three separate runs. Results of the simulations are presented and compared with experimental data and with other recent simulations of POPC and DOPC. Analysis of the hydration environment in the headgroups supports a mechanism by which unsaturation contributes to reduced transition temperatures. In this view, the relatively horizontal orientation of the unsaturated bond increases the area per lipid, resulting in increased water penetration between the headgroups. As a result the headgroup-headgroup interactions are attenuated and shielded, and this contributes to the lowered transition temperature.     

Cutting edge: CD1d deficiency impairs murine host defense against the spirochete, Borrelia burgdorferi

CD1 molecules can present microbial lipid Ag to T cells, suggesting that they participate in host defense against pathogens. In this study, we examined the role of CD1d in resistance to infection with the Lyme disease spirochete, Borrelia burgdorferi (Bb), an organism with proinflammatory lipid Ag. Bb infection of CD1d-deficient (CD1d(-/-)) mouse strains normally resistant to this pathogen resulted in arthritis. Pathology correlated with an increased prevalence of spirochete DNA in tissues and enhanced production of Bb-specific IgG, including IgG to Ag rapidly down-modulated on spirochetes in vivo. CD1d(-/-) mice exhibited high-titer Bb-specific IgG2a, an isotype commonly induced in disease-susceptible mice but not in the disease-resistant control mice in this study. These results show that CD1d deficiency impairs host resistance to a spirochete pathogen, and are the first example of a mutation that imparts Bb-resistant mice with the Ab and disease profile of a susceptible mouse strain.     

Genetically altered mice: phenotypes,no phenotypes,and Faux phenotypes

Phenotype means different things, but whatever the measure, phenotype can be profoundly influenced by genetic, environmental and infectious variables. The laboratory mouse is a complex multisystemic organism which, despite its genetically inbred nature, as highly variable pathophysiologic characteristics. Mouse strains have background characteristics that can influence genomics research. In addition to the mouse itself, different approaches toward creating mutant mice each create variables that influence phenotype. Different background strains of mice are utilized for these different approaches, and various strains are preferred among different laboratories. Background genotype significantly influences phenotype of gene mutations, as can insufficient genetic stabilization of a mutation. Research programs engaged in functional mouse genomics not only must use genetically well-defined mice, but also must incorporate environmental and infectious disease quality assurance/prevention programs. Laboratory mice are subject to over 60 different infectious disease agents, including a wide variety of viruses, bacteria, protozoa, and metazoa. Although these agents can be readily diagnosed and prevented, a number of forces are resulting in their rise in prevalence in mouse colonies. Infectious disease, including clinically silent infections, can and do influence phenotype, and can jeopardize research considerably through lost time, wasted effort, cost, and even loss of valuable strains.