Monitoring longitudinal disease progression in a novel murine Kit tumor model using high-field MRI

Abstract

Animal models are an indispensable platform used in various research disciplines, enabling, for example, studies of basic biological mechanisms, pathological processes and new therapeutic interventions. In this study, we applied magnetic resonance imaging (MRI) to characterize the clinical picture of a novel N-ethyl-N-nitrosourea-induced Kit-mutant mouse in vivo. Seven C3H KitN824K/WT mutant animals each of both sexes and their littermates were monitored every other month for a period of twelve months. MRI relaxometry data of hematopoietic bone marrow and splenic tissue as well as high-resolution images of the gastrointestinal organs were acquired. Compared with controls, the mutants showed a dynamic change in the shape and volume of the cecum and enlarged Peyer´s patches were identified throughout the entire study. Mammary tumors were observed in the majority of mutant females and were first detected at eight months of age. Using relaxation measurements, a substantial decrease in longitudinal relaxation times in hematopoietic tissue was detected in mutants at one year of age. In contrast, transverse relaxation time of splenic tissue showed no differences between genotypes, except in two mutant mice, one of which had leukemia and the other hemangioma. In this study, in vivo MRI was used for the first time to thoroughly characterize the evolution of systemic manifestations of a novel Kit-induced tumor model and to document the observable organ-specific disease cascade.

New C3H KitN824K/WT cancer mouse model develops late-onset malignant mammary tumors with high penetrance

“…Therefore, it is difficult to final conclude, whether the abnormally small cecum found in young mutants is a general feature of this model. However, we were able to confirm this observation in the follow-up disease monitoring study 18 . Similarly, we cannot draw final conclusions concerning the effects of genetic background on tumor development in our model from only four mutant animals investigated in this study.…”

“…In total, five cohorts of heterozygous mutant mice and wild-type littermates were used for the genetic and phenotypic characterization of this mutant line: One cohort of 100 mice on N2-hybrid mixed genetic background for linkage analysis to map the causative mutation, and 4 cohorts on C3H background for the phenotypic characterization: two cohorts of 8-11 mutant and wild-type animals each per sex were used for the two pipeline phenotyping procedure in the German Mouse Clinic (GMC) 47 , one cohort of 10 animals of each sex and genotype Most of the animals used for clinical phenotyping and additional animals from the maintenance breeding colony, from the accompanying disease monitoring study 18 and few animals bred for linkage analysis of the mutation were used for macroscopic and histopathological investigations.…”

Volumetric Printing of Thiol‐Ene Photo‐Cross‐Linkable Poly(ε‐caprolactone): A Tunable Material Platform Serving Biomedical Applications

“…Moreover, when considering the mass and size of the spleen, no increase was observed in any of the groups, which would have been an indication for immune activation (Figures S26 and S27, Supporting Information). [ 53 ] Histopathological evaluation of the implants was then performed, which illustrated that the 3D‐printed constructs were lined by a thin layer of fibroblasts, having a thickness of ≈10–30 µm, in which only limited immune cell infiltration was observed (Figure 6E). In this regard, it should be noted that a minimal foreign body reaction (FBR) is considered beneficial as it leads to the production of growth factors (i.e., VEGF) that are critical in the context of vascularization.…”