Two Siblings of Lewis Rats with a Congenital Homozygous Mutation ofGene Encoding the Large Subunit of Liver-Specific Microsomal TriglycerideTransfer Protein (MTP), Resulting in Pure Red Cell Aplasia and OneSibling with the Heterozygous Genetic Mutation of the Liver MTP Gene

A homozygous sequence mutation of microsomal triglyceride transfer protein (MTP) was studied in three Lewis rat siblings. Two of the three siblings had a homozygous sequence mutation in the exon-1 of the large subunit gene of liver-specific MTP and one of the three siblings had a heterozygous mutation of the large subunit gene. The two rats with a homozygous mutation were confirmed to have pure red cell aplasia at the age of 130 days when they were sacrificed because of weakness. The findings of the two rats were as follows : 1) Body weights were decreased to 65% of normal rats. 2) Plasma apolipoprotein B (apoB) was 0.54-0.60g/L. 3) A homozygous sequence mutation of the large subunit gene of liver-specific MTP was confirmed by polymerase chain reaction (PCR). The specific products of genomic liver DNA were a small amount in the PCR. 4) Acanthocytes constituted 7-14% of the red cells in the peripheral blood (PB). 5) The myeloid to erythroid cell ratio was 10 : 1 in the bone marrow (BM). The BM tended to hypoplasia. 6) Peritubular damage and reduced erythropoietin (epo) secretion were found in the kidney. Amyloid degeneration of the tubules and perivasucular fibrosis were found in the male and the female sibling, respectively. 7) Thymus atrophy with a low % of CD8a+ cells was observed. The silent large subunit gene of genomic lymphocyte DNA was amplified actively in the PCR. 8) Iron was deposited in the small sized hepatocytes with a homozygous MTP gene mutation. In conclusion, silent MTP gene expression and tissue apoptotic changes developed with age in rats with a homozygous liver-specific MTP mutation.