EXPRESSION OF DIFFERENT METALLOTHIONEIN MESSENGER RIBONUCLEIC-ACIDS IN MOTOR CORTEX, SPINAL-CORD AND LIVER FROM PATIENTS WITH AMYOTROPHIC-LATERAL-SCLEROSIS

In earlier studies of sporadic amyotrophic lateral sclerosis (ALS), a disease of unknown etiology, the amount of metallothioneins (MTs), a g roup of small (6-7 kDa) metal-binding proteins, appeared higher in liv er, kidney and spinal cord from patients than from non-neurologic cont rols. Immunohistochemically, the expression of MT in the central nervo us system appeared Limited to glia. Since the highly conserved MTs iso types share antigenic epitopes, they could not be distinguished by imm unological methods. It thus proved necessary to estimate the expressio n of each individual MT messenger ribonucleic acid (mRNA) by performin g reverse transcriptase polymerase chain reaction (RT-PCR)-mediated an alysis of tissue samples. Tissues selected included liver, motor corte x and cervical cord at C6; MT mRNAs analyzed included MT1A, 1B, 1E, 1F , 1G, 2A, and 3. Also, special care was taken to avoid interference by amplification of the 6 MT pseudogenes. Except of MT3, already known a s brain-specific, and MT1B which was not expressed in any tissue, mRNA levels of the other MT genes tended to be higher in ALS than in contr ol liver samples, but the differences did not attain statistical signi ficance. In the nervous system, the diverse MT genes were expressed ov er a greater range in ALS than in controls, but exhibited no change in a consistent direction. At the motor cortex, changes seemed to be les s pronounced than at C6. MT3 was expressed in the motor cortex and the cord. The results provide no evidence for either the induction of a s pecific MT repertoire, or for the inability of glia to express any MT gene in ALS. Because the semi-quantitative RT-PCR technique does not p ermit detailed comparisons between the subtypes of MT expressed in the various tissues, the question whether a single inductor may be held r esponsible for the elevation of MT in the ALS liver and nervous system remains open. In conclusion, ALS tissue remains capable of expressing all the major MT genes. MT, present in protoplasmic glia, arises loca lly and is not secondary to increases of hepatic or renal MT. Because MT3 is also expressed by the normal and ALS spinal cord, it is a centr al nervous system-specific and not only a brain-specific protein. Thus , the excess of MT in ALS liver seems to be an effect of slower catabo lism rather than faster synthesis of protein.