A resistant genetic background leading to incomplete penetrance of intestinal neoplasia and reduced loss of heterozygosity in ApcMin/+ mice

Previous studies of Min/+ (multiple intestinal neoplasia) mice on a sensitive genetic background, C57BL/6 (B6), showed that adenomas have lost heterozygosity for the germ-line ApcMin mutation in the Apc (adenomatous polyposis coli) gene. We now report that on a strongly resistant genetic background, AKR/J (AKR), Min-induced adenoma multiplicity is reduced by about two orders of magnitude compared with that observed on the B6 background. Somatic treatment with a strong mutagen increases tumor number in AKR Min/+ mice in an age-dependent manner, similar to results previously reported for B6 Min/+ mice. Immunohistochemical analyses indicate that Apc expression is suppressed in all intestinal tumors from both untreated and treated AKR Min/+ mice. However, the mechanism of Apc inactivation in AKR Min/+ mice often differs from that observed for B6 Min/+ mice. Although loss of heterozygosity is observed in some tumors, a significant percentage of tumors showed neither loss of heterozygosity nor Apc truncation mutations. These results extend our understanding of the effects of genetic background on Min-induced tumorigenesis in several ways. First, the AKR strain carries modifiers of Min in addition to Mom1. This combination of AKR modifiers can almost completely suppress spontaneous intestinal tumorigenesis associated with the Min mutation. Second, even on such a highly resistant genetic background, tumor formation continues to involve an absence of Apc function. The means by which Apc function is inactivated is affected by genetic background. Possible scenarios are discussed.

Content and quality of 2000 controlled trials in schizophrenia over 50 years

Objective To provide a comprehensive survey of the content and quality of intervention studies relevant to the treatment of schizophrenia.

Tobamovirus and Potyvirus Accumulation in Minor Veins of Inoculated Leaves from Representatives of the Solanaceae and Fabaceae1

Virus invasion of minor veins in inoculated leaves of a host is the likely prelude to systemic movement of the pathogen and to subsequent yield reduction and quality loss. In this study we have analyzed the cell number and arrangement in minor veins within mature leaves of various members of the Solanaceae and Fabaceae families. We then monitored the accumulation pattern of several tobamoviruses and potyviruses in these veins at the time of rapid, phloem-mediated movement of viruses. Vascular parenchyma cells were the predominant and sometimes only cells to become visibly infected among the cells surrounding the sieve elements in minor veins containing 9 to 12 cells. In no instance did we observe a companion cell infected without a vascular parenchyma cell also being infected in the same vein. This suggests that the viruses used in this study first enter the vascular parenchyma cells and then the companion cells during invasion. The lack of detectable infection of smooth-walled companion or transfer cells, respectively, from inoculated leaves of bean (Phaseolus vulgaris) and pea (Pisum sativum) during a period of known rapid, phloem-mediated movement suggests that some viruses may be able to circumvent these cells in establishing phloem-mediated infection. The cause of the barrier to virus accumulation in the companion or transfer cells, the relationship of this barrier to previously identified barriers for virus or photoassimilate transport, and the relevance of these findings to photoassimilate transport models are discussed.