Name: mouse pneumonectomy model of compensatory lung growth
Uploaded: 2014-12-17T14:00:00
Description: Watch this Scientific Journal Video about Mouse Pneumonectomy Model of Compensatory Lung Growth at JoVE.com

The authors would like to acknowledge the Cincinnati Children&#8217;s Hospital Division of Veterinary Services for their assistance. This manuscript was supported by the National Institutes of Health K12 HD028827. Anna Perl PhD taught the authors this surgical procedure.

NOTE: Animal use statement: All procedures in this study were conducted with approval and following the guidelines of the Institutional Animal Use and Care Committee (IACUC) at Cincinnati Children&#8217;s Hospital. Eight week-old C57BL/6J male mice were obtained from Jackson Laboratories (Bar Harbor, ME) and allowed to acclimate for one week prior to use. Up until surgery, animals were housed in a pathogen-free barrier facility and provided autoclaved chow and filtered water ad libdium. Each mouse cage was suppl...

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We have provided the most detailed description of the mouse PNX and mouse sham PNX procedures reported to date. We have made the reader aware of several of the common pitfalls that investigators learning the procedure commonly encounter, and we have outlined several techniques developed by our laboratory to mitigate against these pitfalls. Other laboratories utilizing this model may have developed other technique modifications or use different instruments. When evaluating differences in techniques, individual investigato...

The principal function of the lung is to provide for oxygen and carbon dioxide exchange between an organism and the atmosphere. In humans, a host of congenital and acquired conditions lead to reduced lung surface area which results in impaired lung function. Although a host of therapies such as inhaled corticosteroids, bronchodilators, supplemental oxygen, and chronic mechanical ventilation are used to mitigate the consequences of impaired lung function1-3, the ideal therapy for these conditions would promote regrowth of functional lung tissue &#8211; i.e., lung regeneration.
Mammalian tissue regeneration has been well documented. The African Spiny Mouse can regenerate large areas of skin without scar formation4. The distal phalanx in humans can regenerate following injury or amputation5-7. Following pneumonectomy (PNX), compensatory lung growth occurs in mice8, rats9, dogs10, and humans11. By definition, compensatory lung growth involves not only expansion of existing airspaces, but re-septation of these enlarged airspaces with expansion of the associated microcirculation12. Gene expression analysis has demonstrated that this model recapitulates many of the signaling events of lung development13. Four weeks after mouse PNX, alveolar surface area is equivalent to that of sham operated animals14. In this manuscript, we describe the mouse PNX and sham PNX procedures.

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mouse pneumonectomy model of compensatory lung growth

In humans, disrupted repair and remodeling of injured lung contributes to a host of acute and chronic lung disorders which may ultimately lead to disability or death. Injury-based animal models of lung repair and regeneration are limited by injury-specific responses making it difficult to differentiate changes related to the injury response and injury resolution from changes related to lung repair and lung regeneration. However, use of animal models to identify these repair and regeneration signaling pathways is critical to the development of new therapies aimed at improving pulmonary function following lung injury. The mouse pneumonectomy model utilizes compensatory lung growth to isolate those repair and regeneration signals in order to more clearly define mechanisms of alveolar re-septation. Here, we describe our technique for performing mouse pneumonectomy and sham pneumonectomy. This technique may be utilized in conjunction with lineage tracing or other transgenic mouse models to define molecular and cellular mechanism of lung repair and regeneration.

A plot of PNX and sham operated mouse weights is provided in Figure 6. In our hands, survival is consistently 95 - 100% for both PNX and sham pneumonectomy. For descriptions of how the right lung re-grows in this model and the expected time course, we refer the reader to manuscripts of Gibney et al.15 and Wang et al.14
Several common pitfalls must be avoided to successfully perform the mouse PNX and mouse sham pneumonectomy procedures.</...

Watch this Scientific Journal Video about Mouse Pneumonectomy Model of Compensatory Lung Growth at JoVE.com

Mouse Pneumonectomy Model of Compensatory Lung Growth

Mouse pneumonectomy is a commonly employed model of compensatory lung growth. This procedure can be used in conjunction with lineage tracing or transgenic mouse models to elucidate underlying mechanisms.

In humans, disrupted repair and remodeling of injured lung contributes to a host of acute and chronic lung disorders which may ultimately lead to ...

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