GENOMIC SEQUENCES OF ALDOLASE-C (ZEBRIN-II) DIRECT LACZ EXPRESSION EXCLUSIVELY IN NONNEURONAL CELLS OF TRANSGENIC MICE

Aldolase C is regarded as the brain-specific form of fructose-1,6-bisp hosphate aldolase whereas aldolase A is regarded as muscle-specific. I n situ hybridization of mouse central nervous system using isozyme-spe cific probes revealed that aldolase A and C are expressed in complemen tary cell types. With the exception of cerebellar Purkinje cells, aldo lase A mRNA is found in neurons; aldolase C message is detected in ast rocytes, some cells of the pia mater, and Purkinje cells. We isolated aldolase C genomic clones that span the entire protein coding region f rom 1.5 kb 5' to the transcription start site to 0.5 kb 3' to the end of the last exon, The bacterial gene, lacZ, was inserted in two differ ent locations and the constructs tested in transgenic mice. When the p rotein coding sequences were replaced with lacZ, three of five transge nic lines expressed beta-galactosidase only in cells of the pia mater; one line also expressed in astrocyte-like cells, When lacZ was insert ed into the final exon (and all structural gene sequences were retaine d) transgene expression was observed in astrocytes in all regions of t he central nervous system as well as in pial cells, Thus, with the exc eption of Purkinje cell expression, the behavior of the full-length tr ansgene mimics the endogenous aldolase C gene. The results with the sh orter transgene suggest that additional enhancer elements exist within the intragenic sequences. The absence of Purkinje cell staining sugge sts that the cis elements required for this expression must be located outside of the sequences used in this study.