A homozygous and a heterozygous defect of the winged helix DNA-binding domain of the fork head (FH) gene in tailless and tailed rat siblings: resultant lymphocyte-rich thymoma connected with renal tubule amyloid β (Aβ) deposits

Abstract

Objective To investigate the cause of thymoma connected with renal amyloid β (Aβ) overproduction. Design and methods Pathologic, immune-fluorescence analyses, flow cytometry (FCM) analyses, polymerase chain reaction (PCR) and reverse transcriptase (RT)-PCR were applied for tailless and tailed Lewis/Sea rat siblings at the age of 6 months. Results A homozygous defect of the winged helix DNA-binding domain of the fork head (FH) gene was detected in the RT-PCR of the tailless rat kidney and liver. Lymphocyte-rich thymoma was found in both rats, but was more prominent in the tailless rat. FCM showed that CD4+ and CD8a+ cells constituted of more than 90% of the thymus lymphocytes in both rats. Aβ deposits in the renal tubules of both rats were shown by positive staining with antihuman Aβ (11–28) antibody (Ab) together with the activation of the kidney presenilin (PSEN) genes. The mRNA level of transthyretin (TTR) was suppressed moderately with age by the homozygous FH1 gene defect. Conclusion Both homozygous and heterozygous defects of the DNA-binding domain of the FH gene caused lymphocyte-rich thymoma and renal Aβ overproduction.