Cockayne syndrome (CS) is an autosomal recessive disorder, which is associated with abnormal UV hypersensitivity, growth retardation, and psycho-neural abnormalities. Recently, CSA protein was found to be associated with CS. We obtained mRNAs from immortal lymphoblasts derived from members of the kindred, and sequenced the CSA gene of all family members after reverse transcription (RT) of the coding region. The intact length of the CSA transcript was found in all family members except the proband with CS. Multiple abnormal splicing variant forms were revealed in all cases. No mutation was found in the sequences of the splice donor and acceptor sites of each exon in the CSA gene. UVA irradiation suppressed cell growth in the proband. There was no significant alteration of UVA sensitivity among the normal control and the family members except for the proband. These data suggest that multiple splicing variant forms of CSA mRNA, in the absence of the full-length form of the mRNA, are associated with CS.

We have previously shown that cytosolic 3,5,30 -triiodo-L-thyronine (T3)-binding protein (CTBP) possesses a high affinity for T3 binding in the presence of nicotinamide adenine dinucleotide phosphate in vitro, and that p38CTBP increases intracellular content of T3, and suppresses T3-mediated transactivity. Screening of mRNA expression in 73 different human tissues has demonstrated that p38CTBP mRNA is expressed at high levels in brain and heart. We have examined the intracellular localization and tissue-specific distribution of this protein by using a specific antibody against human p38CTBP. Western blotting and immunoprecipitation studies have shown that the antibody recognizes human p38CTBP. Interaction of p38CTBP with the antibody did not affect the T3-binding activity of p38CTBP, and its dimer formation in vitro. Western blotting analysis has shown that p38CTBP is expressed in brain and heart predominantly, similar to the distribution of mRNA. Immunohistochemical studies have demonstrated p38CTBP in neural cells and cardiac muscle cells. p38CTBP localizes in cytoplasm rather than in nuclei in neural cells. The evidence for the presence of tissue-specific localization of p38CTBP has indicated that p38CTBP has a tissue-specific function, such as the regulation of T3 delivery from cytoplasm to nuclei.

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