Methylated lysine in storage body protein of sheep with hereditary ceroid-lipofuscinosis.

Juvenile ceroid-lipofuscinosis (Batten disease) is a hereditary storage disease with an autosomal-recessive mode of transmission. This disorder has been identified in humans, dogs and sheep. It is characterized by massive accumulations of autofluorescent storage bodies in many tissues. This storage body accumulation is accompanied by functional decline and degeneration of the affected tissues, and ultimately results in premature death. The primary defect responsible for juvenile ceroid-lipofuscinosis has not been identified. Previous studies have indicated that the storage material is primarily protein. Why this protein accumulates in storage bodies remains to he determined. In affected humans, the storage body protein appears to be abnormally rich in a methylated derivative of lysine (epsilon-N-trimethyllysine). Studies were undertaken to determine whether the storage bodies from sheep with hereditary ceroid-lipofuscinosis were also characterized by the presence of this modified amino acid. Chromatographic and mass spectral analyses of hydrolysates of the storage body protein indicated a significant fraction of the lysine residues in this protein were present as the epsilon-N-trimethyl derivative. This modified amino acid was not detected in hydrolysates of protein from normal sheep tissues or from tissues of sheep with GM1 gangliosidosis, nor did it appear to be present in the storage body protein from a human subject with the late infantile form of ceroid-lipofuscinosis. Thus, it is apparently specific to the storage body protein that accumulates in the juvenile type of this disease. The abnormal presence of epsilon-N-trimethyllysine in proteins could interfere with their sorting or degradation within cells and thus cause them to accumulate in the storage bodies characteristic of the human juvenile and ovine ceroid-lipofuscinoses.