Model For Investigation Of Pathogenesis Research Articles

A Possible Murine Model for Investigation of Pathogenesis of Sudden Infant Death Syndrome

Several studies have indicated a possible causative role of toxigenic bacteria in sudden infant death syndrome (SIDS). This study examined the effect of toxigenic E. coli on pregnant and infant mice to determine if these animals could be used as a model for SIDS pathogenesis. Strains of E. coli from the intestinal contents of infants who have died of SIDS or other causes and from the faeces of healthy infants were collected over a broad time scale. The isolates were tested for their ability to produce then known toxins of E. coli and were serotyped (O and H antigens). Certain serotypes (e.g. O1:H- and O25:H1) emerged significantly more frequently from cases of SIDS than from healthy infants and isolates of these types were generally toxigenic in Vero-cell cultures but whose verotoxicity was not related to classical Shiga or other known toxins. This mouse model was developed to test the effects of these toxigenic and also non-toxigenic strains. Four apparently healthy pups aged between 17 and 21days died unobserved overnight but no pups of the 54 control mice died suddenly (P=0.0247, Fisher's exact test). These were considered to represent sudden unexpected deaths. Pathological effects compatible with those in SIDS were observed in mouse pups exposed to toxigenic strains indicating this model may be suitable for further study into the pathogenesis of unexpected deaths in infancy. Providing an animal model of SIDS would promote a much better avenue for studying the pathogenesis of this enigmatic condition.

Vertical transmission of murine gammaherpesvirus 68 in mice

The mouse infected with murine gammaherpesvirus 68 (MHV-68) is accepted animal model for investigation of pathogenesis, oncogenesis, immunology and molecular biology of gammaherpesviruses in their natural host. However, little is known about the host range, epidemiology and pathogenesis of this natural pathogen of free-living murid rodents. Therefore we addressed the question of transplacental transmission of MHV-68 from pregnant Balb/c mice chronically infected with the virus to their fetuses and shedding of the virus by breast milk from chronically infected mothers to their offspring. The mothers were positive to infectious virus and viral antigen in various organs but mainly in the spleen and peritoneal *macrophages. Virus-neutralizing serum antibodies, and leukocyte count with a proportion of atypical lymphocytes were increasing to elevated values with the time of infection. The chronic infection resulted in premature termination of pregnancy or reduced number and size of newborns due to their retarded development. Out of 10 infected pregnant mice just one died and another developed a tumor. All these results confirm the vertical transmission of MHV-68 in mice, teratogenicity of the virus and the virus shedding by breast milk.

α-Mannosidosis in the guinea pig: cloning of the lysosomal α-mannosidase cDNA and identification of a missense mutation causing α-mannosidosis

α-Mannosidosis is a lysosomal storage disorder caused by deficient activity of the lysosomal α-mannosidase. We report here the sequencing and expression of the lysosomal α-mannosidase cDNA from normal and α-mannosidosis guinea pigs. The amino acid sequence of the guinea pig enzyme displayed 82–85% identity to the lysosomal α-mannosidase in other mammals. The cDNA of the α-mannosidosis guinea pig contained a missense mutation, 679C>T, leading to substitution of arginine by tryptophan at amino acid position 227 (R227W). The R227W allele segregated with the α-mannosidosis genotype in the guinea pig colony and introduction of R227W into the wild-type sequence eliminated the production of recombinant α-mannosidase activity in heterologous expression studies. Furthermore, the guinea pig mutation has been found in human patients. Our results strongly indicate that the 679C>T mutation causes α-mannosidosis and suggest that the guinea pig will be an excellent model for investigation of pathogenesis and evaluation of therapeutic strategies for human α-mannosidosis.