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.
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 alpha 1-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 alpha 1-antitrypsin (AT) in the rough endoplasmic reticulum (RER). Large, defined accumulations of alpha 1-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 alpha 1-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.
Nakatsuji
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Department of Transfusion, Hamamatsu University School of Medicine, Japan.
D000818:Animals; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D010455:Peptides / Q000235:genetics*; D051381:Rats; D011917:Rats, Inbred Lew
D047908:Intracellular Signaling Peptides and Proteins; D010455:Peptides; C086598:lambda Spi-2