The ROSA26 LacZ-neo R insertion confers resistance to mammary tumors in Apc Min/+ mice

B6.129S7-Gtrosa26 (ROSA26) mice carry a LacZ-neo ^R insertion on Chromosome (Chr) 6, made by promoter trapping with AB1 129 ES cells. Female C57BL/6J Apc ^Min /+ (B6 Min/+) mice are very susceptible to the induction of mammary tumors after treatment with ethylnitrosourea (ENU). However, ENU-treated B6 mice carrying both Apc ^Min and ROSA26 are resistant to mammary tumor formation. Thus, ROSA26 mice carry a modifier of Min-induced mammary tumor susceptibility. We have previously mapped the modifier to a 4-cM interval of 129-derived DNA that also contains the ROSA26 insertion. Here we report additional evidence for the effect of the ROSA26 insertion on mammary tumor formation. To test the hypothesis that the resistance was due to a linked modifier locus, we utilized two approaches. We have derived and tested two lines of mice that are congenic for 129-derived DNA within the minimal modifier interval and show that they are as susceptible to mammary tumors as are B6 mice. Additionally, we analyzed a backcross population segregating for the insertion and show that mice carrying the insertion are more resistant to mammary tumor development than are mice not carrying the insertion. Thus, the resistance is not due to a 129-derived modifier allele, but must be due to the ROSA26 insertion. In addition, the effect of the ROSA26 insertion can be detected in a backcross population segregating for other mammary modifiers. Received: 29 December 2000 / Accepted: 4 April 2001     

Differentiation of mesothelial cells during their reparative regeneration

The investigation on regenerative processes of mesothelium of the parietal peritoneum was performed in 120 white mice under the effect of certain irritants producing lesions various in depth and intensity. Nuclear-cytoplasmic relations and ultramicroscopic cellular rearrangement were studied during the process of differentiation of the mesothelial regenerate. Two periods of the regenerative process are stated and it is demonstrated that rearrangement of the mesothelial cells and the mode of their division depend on intensity of the lesions. When the peritoneal lesion is severe, at the first stages of regeneration (the 1st period) rearrangement of cells towards their hypertrophy and increased functional activity is predominant in the mesothelium. Further (the 2d period), the number of mitotically dividing cells is increasing in the mesothelial regenerate and in rearrangement of the mesothelial cells the processes connected with a partial loss of their signs of specialization predominate. The transition from one period into another is gradual and duration of each depends on intensity of the lesion.     

The mechanisms of reparative regeneration of venous endothelium

The reaction of endothelial cells of the inferior vena cava in response to freezing-induced lesions has been analysed in the experiments on 34 young adult Kyoto-Wistar normotensive rats. First the de-endothelialized surface is covered with flattened platelets and then, three days after surgery, the endothelium is restored as a result of migration and proliferation of endotheliocytes. The migrating endothelial cells removed the adhered platelets from de-endothelialized surface. The young endothelium was presented by a single layer of strongly elongated endothelial cells whose axis was parallel to the flow of blood. An immature endothelium is characterized by an increased number of endotheliocytes. No essential differences in the reaction of venous and aortic endothelium have been revealed in response to freezing-induced lesions.     

Physiological and reparative regeneration of the mitochondria]

The ultrastructure of mitochondria of hepatocytes in normal and pathological conditions was studied. It was shown that the process of regeneration of the ultrastructure of swollen mitochondria with a lucent matrix up to the normal state was completed in hepatocytes of the rat and chick embryos within one day. It was established that one of the ways of intraorganoid regeneration of mitochondria in hepatocytes of chick embryos and of mice after injections of CCl4 twice a week for 5 months was clasmatosis of the destroyed mitochondria fragments and their removal through the partially disintegrated exterior membrane of mitochondria followed by the membrane restoration. The process of mitochondrial regeneration after clasmatosis of its fragments was shown to require two days in the chick embryo hepatocytes.     

Venous graft-derived cells participate in peripheral nerve regeneration

Background

Based on growing evidence that some adult multipotent cells necessary for tissue regeneration reside in the walls of blood vessels and the clinical success of vein wrapping for functional repair of nerve damage, we hypothesized that the repair of nerves via vein wrapping is mediated by cells migrating from the implanted venous grafts into the nerve bundle.

Methodology/Principal Findings

To test the hypothesis, severed femoral nerves of rats were grafted with venous grafts from animals of the opposite sex. Nerve regeneration was impaired when decellularized or irradiated venous grafts were used in comparison to untreated grafts, supporting the involvement of venous graft-derived cells in peripheral nerve repair. Donor cells bearing Y chromosomes integrated into the area of the host injured nerve and participated in remyelination and nerve regeneration. The regenerated nerve exhibited proper axonal myelination, and expressed neuronal and glial cell markers.

Conclusions/Significance

These novel findings identify the mechanism by which vein wrapping promotes nerve regeneration.     

Radiation-induced concomitant overexpression of p53, p62c-fos and p21N-fas in mouse epidermis

Abstract. Early molecular events in radiation carcinogenesis in vivo are difficult to study, especially because it is usually impossible to know in advance the exact location of a radiation-induced tumour. In the present study, we have attempted to overcome this difficulty by exposing a very small area of hairless mouse skin to high-dose beta radiation (i.e. immobilized hot particles) on the reasonable assumption that a malignant tumour would subsequently develop and be found at the exposed site in a long-term follow-up. The results showed that at an exposed site, before the appearance of a visible or histologically detectable tumour, overexpression of the product of the tumour suppressor gene p53 was common (28% of the sites studied; tested with PAbl801, PAb421, PAb240 and a polyclonal antibody CM1) and that this change was regularly accompanied by overexpression of p62^c-fos and p21^N-ras. Expression of several other oncoproteins studied (p39^c-jun, p21^K-ras, p21^H-ras) was not altered at these sites. A similar pattern of changes was observed in a visible and histopathologically distinct tumour that was analyzed after its development at an exposed site. These results suggest a re'markably regular pattern of molecular changes, induced by ionizing radiation in mouse epidermis, which might be associated with carcinogenesis.     

New insights on the reparative cells in bone regeneration and repair

Bone possesses a remarkable repair capacity to regenerate completely without scar tissue formation. This unique characteristic, expressed during bone development, maintenance and injury (fracture) healing, is performed by the reparative cells including skeletal stem cells (SSCs) and their descendants. However, the identity and functional roles of SSCs remain controversial due to technological difficulties and the heterogeneity and plasticity of SSCs. Moreover, for many years, there has been a biased view that bone marrow is the main cell source for bone repair. Together, these limitations have greatly hampered our understanding of these important cell populations and their potential applications in the treatment of fractures and skeletal diseases. Here, we reanalyse and summarize current understanding of the reparative cells in bone regeneration and repair and outline recent progress in this area, with a particular emphasis on the temporal and spatial process of fracture healing, the sources of reparative cells, an updated definition of SSCs, and markers of skeletal stem/progenitor cells contributing to the repair of craniofacial and long bones, as well as the debate between SSCs and pericytes. Finally, we also discuss the existing problems, emerging novel technologies and future research directions in this field.