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 beta (Abeta) deposits.

OBJECTIVE

To investigate the cause of thymoma connected with renal amyloid beta (Abeta) 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. Abeta deposits in the renal tubules of both rats were shown by positive staining with antihuman Abeta (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.

CONCLUSIONS

Both homozygous and heterozygous defects of the DNA-binding domain of the FH gene caused lymphocyte-rich thymoma and renal Abeta overproduction.