Serpina1^em2Chmu

CRISPR/Cas9 technology is used to disrupt five highly homologous gene paralogs through the targeting of exon 2 using a combination of four gRNAs, deleting 55 kb (103767258-103822011) and 90 kb (103858249-103947696), resulting in the excision of Serpina1d and Serpina1a and 1c. In addition, complementary targeted locus amplification sequencing shows a 73-bp deletion in exon 2 of Serpina1b, causing a frameshift and a truncated protein that is predicted to be 105 amino acids instead of 413. Transcriptome analysis indicates unchanged levels of transcripts. Western blot confirmed absence of the alpha1-antitrypsin protein in serum. (J:259615)