Transgenic and gene-targeted mice as models for chronic obstructive pulmonary disease: Fig. 1—

Abstract

Animal models play an important role in the understanding of the pathogenesis of chronic obstructive pulmonary disease (COPD). The applicability of findings to human COPD depends upon several factors, including the disease model, and similarities in mouse structure and function between species.There are many examples in the literature of transgenic mice that have contributed to the understanding of COPD. Several studies demonstrate the complexity of inflammatory networks and how unexpected findings in animal models have led to the search for new potential mediators in human disease.Gene-targeting studies into a 1 -antitrypsin (a 1 -AT) and emphysema in mice have demonstrated that the genetic locus for a 1 -AT in mice is very complex and that the loss of one gene is lethal in embryo lung development. This underlines the differences between mice and humans that limit the ability to translate between systems in some instances. Gene targeting has also highlighted complex roles for transforming growth factor-b in COPD and has been used to determine important molecules and pathways in COPD.Both transgenic and gene-targeted models suffer limitations and their applicability to human chronic obstructive pulmonary disease may be dependant on several factors, some of which are still being learnt. The more that is known about similarities and differences, the better the knowledge will be that is gained to develop for chronic obstructive pulmonary disease.

Genetically manipulated mouse models of lung disease: potential and pitfalls

“…In addition, genes that are important in the development of COPD in humans are not always expressed in mice, thus prompting some investigators to develop genetically modified mice that overexpress human genes (e.g., see MMP-1 mice in Supplemental Table S1). Although we have chosen to focus on murine models of COPD that arise from cigarette exposure, there are clearly other conditions (genetic and environmentally mediated) that lead to COPD, and thus translatability of findings in one model must be applied with caution to all forms of the disease (135).…”

Animal models of pulmonary emphysema: a stereologist's perspective

“…With the establishment of transgenic mouse technologies, a number of candidate genes thought to be involved in the pathogenesis of COPD and emphysema have been studied by generating mice that are either deficient in or overexpress the gene of interest, as has been comprehensively reviewed [8,[42][43][44]. When studying mutants or transgenic animals, the analysis of the time course of the formation of an emphysema-like phenotype is of major importance to distinguish developmental defects [45] that result in the impairment of alveolarisation, from the loss of (already formed) mature alveoli, which is characteristic of human pulmonary emphysema [44].…”

“…When studying mutants or transgenic animals, the analysis of the time course of the formation of an emphysema-like phenotype is of major importance to distinguish developmental defects [45] that result in the impairment of alveolarisation, from the loss of (already formed) mature alveoli, which is characteristic of human pulmonary emphysema [44].…”

New ways in respiratory genetics

“…Cell-specific transgenic mice models allow very specific pathways to be distinguished. Using examples from the field of COPD, SHAPIRO [6] illustrates how animal models can be used to dissect disease pathways in vivo and have already increased our knowledge about genetic influences in lung structure and development.…”

“…SHAPIRO [6] takes a critical look at animal models and their use in respiratory genetics. Even though translation from mouse to human requires caution, a lot can be learned from transgenic and gene-targeted mice for respiratory diseases.…”