Increased mutation frequency and altered spectrum in one of four thymic lymphomas derived from tumor prone p53/Big Blue double transgenic mice.

p53 (-/-), lacI (+/-) double transgenic (p53/Big Blue3) mice provide an opportunity to examine the relationship in vivo between somatic mutation and tumorigenesis. Previously, the frequency and spectra of lacI mutations were found to be similar in normal tissues of 6 week old p53 (-/-) lacI (+/-) and p53 (+/+) lacI (+/-) mice. Herein, p53 (-/-), lacI (+/-) mice were used to examine the frequency and spectrum of spontaneous mutation in thymic lymphomas. Four mice with thymic lymphomas were sacrificed at 2.5, 3, 4 and 4.5 months of age. Normal thymus harvested from two p53 (+/+) lacI (+/-) mice and two p53 (-/-) lacI (+/-) mice served as controls. The mutation frequency in tumor 108 (6.8 x 10(-5)) was elevated 2.3-fold relative to the p53 (-/-) control (P<0.0001; chi2 test). The mutation spectra were also different (P=0.0009; Fisher exact test); in particular, A:T-->G:C transitions were prominently overrepresented in tumor 108. In addition, there were two examples of unusual deletions with inversions. In tumors 44 and 115, but not 110, there were trends toward increased mutation frequencies and altered spectra, but, within the constraints of present sample sizes, the results are not statistically significant. In conclusion, these findings suggest that altered frequencies and spectra exist in a subset of thymic lymphomas, perhaps due to somatic mutation in one or more DNA repair genes.

p53 wild-type and p53 nullizygous Big Blue transgenic mice have similar frequencies and patterns of observed mutation in liver, spleen and brain.

Transgenic mouse mutation detection systems offer a powerful tool for analysis of spontaneous and induced mutations in vivo. Mice doubly transgenic for a null mutation of the p53 tumor suppressor gene and a lambda shuttle vector harboring the lacI gene were utilized to examine the rate and pattern of spontaneous somatic mutation of the lacI transgene in vivo. Three somatic tissues were examined: liver, spleen and brain. At 6 weeks of age, three p53 wild type (+/+) and three p53 nullizygous (-/-), lacI (+/-) male mice were analysed. The mutation frequencies in the two genotypes were similar. The mutant frequencies for wild type (+/+) and nullizygous (-/-) p53 genotypes were, respectively, 4.2 x 10(-5) and 3.6 x 10(-5) in the liver, 4.3 x 10(-5) and 3.4 x 10(-5) in the spleen and 2.8 x 10(-5-) and 3.0 x 10(-5) in the brain. When the data from the three tissues were combined, the mutant frequency was 3.7 x 10(-5) for the (+/+) genotype and 3.3 x 10(-5) for the (-/-) genotype. By sequencing both strands in the DNA-binding region of the lacI gene, 91 mutations were found. When recurrent mutations in the same mouse were excluded, a total of 67 definitely independent mutations were found. No statistically significant differences were found in the mutational spectra between the two genotypes when the three tissues were analysed individually or combined (P = 0.58). These findings suggest a need to reconsider the general form of hypothesis that the p53 gene serves as the 'guardian of the genome'.

Clinical, pathologic, and serologic features of an epizootic of mousepox in Minnesota.

An epizootic of mousepox in two colonies of mice was described. Clinical signs, morbidity and mortality rates, and necropsy lesions were substantially influenced by husbandry practices, intercurrent diseases (Sendai pneumonia, mouse hepatitis virus), and total body x-irradiation. In one colony, 54 mice were necropsied; 19 mice had cutaneous or visceral lesions of mousepox although none had combined visceral and cutaneous lesions. In the other colony, 20 mice were necropsied, and 10 mice had cutaneous lesions; none had visceral lesions. Sera from 24 mice with the cutaneous form of the disease had no demonstrable HI antibody titer. Experimental mice injected with spleen/liver homogenates from infected colony mice developed typical visceral lesions with numerous poxvirus profiles on electron micrographs and positive HI titers. Mice immunized with vaccinia virus were not susceptible to the disease.

Hamster (Mesocricetus auratus) enteritis caused by epithelial cell-invasive Escherichia coli.

When inoculated orally, Escherichia coli strain 1056 caused acute enteritis in 7 of 22 weanling hamsters. E. coli strain 1056 was isolated from the ileum of a hamster with proliferative ileitis. It was lactose negative, nonmotile, and anaerogenic. By electron microscopy and indirect fluorescent-antibody techniques, E. coli strain 1056 was detected in absorptive epithelial cells, resembling invasive E. coli and shigella infections of other species. Ileitis did not progress to epithelial cell hyperplasia, which is characteristic of proliferative ileitis of hamsters. A control group of 10 hamsters, inoculated with nonenteropathogenic E. coli isolated from a normal hamster, did not develop signs or lesions.

Rapid methods for jugular bleeding of dogs requiring one technician.

Two methods were used to collect blood from the jugular vein of dogs. In both techniques, only one technician was required. A rope with a slip knot was placed around the base of the neck to assist in restraint and act as a tourniquet for the vein. The technician used one hand to restrain the dog by the muzzle and position the head. The other hand was used for collecting the sample. One of the methods could be accomplished with the dog in its cage. The bleeding techniques were rapid, requiring approximately 1 minute per dog.

An ovarian teratoma in a guinea pig.

An ovarian teratoma was diagnosed in a one-year-old, virgin female, Strain 13 guinea pig that died unexpectedly. The left ovary was replaced by a 5.5 x 5 x 3 cm mass. Microscopically, dense fibrous connective tissue, immature neuroepithelium, central and peripheral nervous tissue, respiratory epithelium and cartilage were observed. A similar mass, 1.2 x 1 x 1 cm, composed largely of embryonal neural tissue, was adhered to the abdominal side of the diaphragm. The latter mass probably resulted from transcoelomic seeding by the ovarian tumor.

Enteropathogenicity of Escherichia coli isolated from hamsters (Mesocricetus auratus) with hamster enteritis.

Escherichia coli isolated from ilea of hamsters with hamster enteritis were tested for enteropathogenicity in intestinal loops prepared in both adult and weanling hamsters. E. coli isolated from hamsters with hamster enteritis caused dilatation of loops in weanling hamsters but not in adult hamsters.

Experimental hamster enteritis: an electron microscopic study.

Hamster enteritis (HE) was experimentally produced in weanling hamsters by orally inoculating healthy hamsters with suspensions of ilea obtained from hamsters with HE. Control groups of hamsters were inoculated orally with suspensions of ilea from healthy hamsters. Electron microscopy was done on ilea from 6 control hamsters, 31 hamsters with experimentally produced HE, and 4 hamsters with naturally occurring HE. Ultrastructural changes were not observed in the absorptive epithelium of control animals. Two different intracytoplasmic bacterial organisms were observed in epithelial cells of hamsters with experimentally produced HE. Organisms that were observed early in the disease process were identified as Escherichia coli. Organisms ultrastructurally similar to Campylobacter spp were observed later in the disease and were only within hyperplastic epithelial cells. The hyperplastic ileal epithelium of hamsters with naturally occurring HE contained campylobacter-like organisms.

Unusual aggressive behavior in the male golden hamster.

An unusually aggressive male golden hamster (Mesocricetus auratus) removed flank glands from other adult male hamsters by biting. Females and immature males were not attacked. No underlying abnormality to account for this aberrant behavior was evident.