The role of mouse strain differences in the susceptibility to fibrosis: a systematic review

Abstract

In humans, a number of genetic factors have been linked to the development of fibrosis in a variety of different organs. Seeking a wider understanding of this observation in man is ethically important. There is mounting evidence suggesting that inbred mouse strains with different genetic backgrounds demonstrate variable susceptibility to a fibrotic injury. We performed a systematic review of the literature describing strain and organ specific response to injury in order to determine whether genetic susceptibility plays a role in fibrogenesis. Data were collected from studies that were deemed eligible for analysis based on set inclusion criteria, and findings were assessed in relation to strain of mouse, type of injury and organ of investigation. A total of 44 studies were included covering 21 mouse strains and focusing on fibrosis in the lung, liver, kidney, intestine and heart. There is evidence that mouse strain differences influence susceptibility to fibrosis and this appears to be organ specific. For instance, C57BL/6J mice are resistant to hepatic, renal and cardiac fibrosis but susceptible to pulmonary and intestinal fibrosis. However, BALB/c mice are resistant to pulmonary fibrosis but susceptible to hepatic fibrosis. Few studies have assessed the effect of the same injury stimulus in different organ systems using the same strains of mouse. Such mouse strain studies may prove useful in elucidating the genetic as well as epigenetic factors in humans that could help determine why some people are more susceptible to the development of certain organ specific fibrosis than others.

Characterisation of the mechanical properties of infarcted myocardium in the rat under biaxial tension and uniaxial compression

“…Although Clarke et al [34] recently suggested that the collagen fibre structure and the mechanical properties of infarcted tissue could vary between studies employing the same animal model, the reason behind this variation is not very well understood. Nevertheless, the discrepancy between our results and that of Fomovsky and Holmes [20] could potentially be attributed to the difference in animal strain [35,36]. It could also be due to the variation in the amount of isolated muscle fibres especially when considering the difficulty of precisely controlling the size of the infarct in the samples as we demonstrated in this study.…”

Neuregulin-1 attenuates development of nephropathy in a type 1 diabetes mouse model with high cardiovascular risk

“…Although various studies have shown myocardial fibrosis and apoptosis in different models of diabetic cardiomyopathy, other investigators have observed the absence of fibrosis and apoptosis (32). Variability in the degree of myocardial fibrosis and apoptosis in diabetic rodent models has been explained by differences in animal species (2), differences in mouse strains (41), variable levels of hyperglycemia (39), differences in compensatory upregulations of metalloproteinases (43), and differences in the effects of STZ (7), the last of which may cause nonspecific toxicity besides pancreatic injury and includes tissue apoptosis. Importantly, in our study, all cardiac changes in apoE Ϫ/Ϫ mice were prevented by insulin, supporting that hyperglycemia, rather than nonspecific STZ toxicity, was the responsible factor.…”

Macrophage Overexpressing NGAL Ameliorated Kidney Fibrosis in the UUO Mice Model

“…Adoptive transfer of cells to mouse with different H-2 antigen is possibly immunogenic. The mice strain usually used to study chronic kidney damage is C57BL6 based on its susceptibility to renal fibrosis [34]. On the other hand, to achieve a stable φ-NGAL transduction, we used the commercial cell line RAW264.7.…”