One Lewis Rat with Homozygous Defect of the Serine Proteinase Inhibitor 2 (Spi-2) Gene and Two Lewis Rats with Heterozygous Spi-2 Gene Defect

Abstract

One LEW/Sea (Lewis) strain rat, Rat P-1, had a homozygous defect of the serine proteinase inhibitor 2 (Spi-2) gene coding for serpin contrapsin. A sibling, Rat P-2, and a rat of the same strain, Rat P-3, had a heterozygous Spi-2 gene defect. The homozygous Spi-2 gene defect of Rat P-1 was diagnosed by the polymerase chain reaction (PCR). The presence of an α1-proteinase inhibitor (PI) gene was confirmed by PCR in all 3 rats. Rat P-1 and the sibling Rat P-2 were sacrificed at 7 days of age because of the severe weakness of Rat P-1, although Rat P-2 appeared healthy. Rat P-3 was sacrificed at 40 days of age because of the severe weakness. Rat P-1's hepatocytes with the homozygous Spi-2 gene defect showed massive accumulation of polymerized α1-antitrypsin (AT) in the rough endoplasmic reticulum (RER). Large, defined accumulations of α1-AT were not found in the heterozygous rats with the Spi-2 gene defects. Nephrogenesis was retarded in all 3 rats, especially in Rat P-1. Extramedullary hematopoiesis was absent in the liver of Rat P-1 and suppressed in the spleen of Rat P-3, where activated α1-AT synthesis was found. Atelectasis mixed with hyperinflated lung regions and thymic apoptosis were observed in the 2 weak rats. As Spi-2 gene defect had some similar clinical points to platelet-derived growth factor (PDGF) deficiency, it was suggested that increased vasoconstrictor peptide hormones competed with PDGF for binding to the PDGF-receptors.