The Effect of Trisomy-21 (Down’s Syndrome) on Brain Transcription

Messenger RNA from foetal, brains of normal and Down’s syndrome subjects was translated in vitro, Trisomy-21 resulted in a significant increase in the mRNA for a 68 kD microtubule-associated protein (68K MAP). This protein, whose gene thus putatively maps to chromosome 21, is a component of synaptic structures and membranes. An imbalance in its synthesis during brain development could contribute to the abnormal brains characteristic of Down’s syndrome. The 68K MAP is homologous to a constitutively synthesized 76 kD member of the heat-inducible family of proteins (heat-shock or stress proteins). However, in human ftbro- blasts, the amount of 68K MAP synthesized was not dependent on the content of chromosome 21, in contrast to that of another heat-inducible, but constitutive 74 kD protein. These results indicate that the effect of trisomy-21 on mRNA levels is tissue-specific and that chromosome 21 may be involved in stress responses in addition to cytoskeletal functions.