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.
Highlights
In humans, a number of genetic factors have been linked to the development of fibrosis in a variety of different organs
We summarise the evidence from murine studies performed to assess fibrosis in different organs, and we discuss the influence of mouse strain on the susceptibility to fibrosis in these organs
Significant straindependent differences were seen in the architecture of the colon between the strains but not in the levels of TGF-β1, 2, 3 or Tumor necrosis factor alpha (TNF-α) [24]. These results support the findings demonstrated in models of pulmonary fibrosis due to irradiation
Summary
This systematic review has shown that there are differences in susceptibility to develop fibrosis in various inbred mouse strains. Phenotypes measured in varying strains can act as a base for genetic studies to determine the variation that causes a specific phenotype to develop and predisposes an individual to a disease, in this case fibrosis These mouse studies are complimentary to human association studies and allow the analysis firstly of the clinical disease and of the genetic variants that are associated with the disease to be assessed in a controlled environment [88]. Organs in the same inbred strain of mouse share the same DNA sequence, yet exhibit widely differing structure and function, demonstrating major epigenetic control of gene expression in normal development and physiology. The observation that there are different susceptibilities of various organs to fibrosis within the same mouse strain highlights epigenetic control as an important modulator of fibrotic response. Regeneration of amputated digit tips was investigated in MRL mice, and digits were found to re-grow with partial reformation of nails significantly more than the other strains, C57BL/6 and DBA/2 mice [92]
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