Faculty Advisor

Heilman, Destin

Project Center

University of Massachusetts Medical Center


Alpha-1 Antitrypsin Deficiency is a genetic disease characterized by low plasma levels of Alpha-1 Antitrypsin (AAT), an inhibitor that protects the alveolar matrix. Low levels of AAT, lead to emphysema, yet an animal model simulating the lung condition didn’t exist. Recently Mueller et al used CRISPR/Cas9 to create a quintuple knockout of the SERPINA1 gene. Here I prove the mouse model created is a complete knockout (KO). No AAT was found in sera of the KOs and there was no inhibition of neutrophil elastase. Also, KO animals developed emphysema after treatment with LPS (a model that simulates bacterial infection), indicating AAT KO. This will serve as the first AAT-deficient model for the lung and could serve as a model for COPD, allowing for discovery of potential treatments.


Worcester Polytechnic Institute

Date Accepted




Project Type

Major Qualifying Project


Restricted-WPI community only

Advisor Department

Chemistry and Biochemistry

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