Structure and chromosomal localization of the human and mouse muscle fructose-1,6-bisphosphatase genes

Mammalian skeletal muscle contains fructose-1,6-bisphosphatase (Fru-1,6-P(2 )ase), a key enzyme of glyconeogenesis. We have shown previously that muscl e Fru-1,6-P(2)ase is encoded by a gene different from that coding for the l iver isoenzyme. Starting with genomic YAC libraries and based on the cDNA s equences of human and mouse muscle Fru-1,6-P(2)ases together with the known gene structures of two mammalian liver fructose-1,6-bisphosphatases, we ha ve PCR-amplified and sequenced all functional parts of the human and mouse muscle fructose-1,6-bisphosphatase genes and determined their chromosomal l ocalization. The human gene (FBP2), localized at chromosome 1p36.1-2, spans about 30 kb, while the mouse gene (Fbp2) at chromosome 13B3-Cl is more com pact (about 21 kb), Intron lengths are only poorly conserved between the tw o genes, while intron number and positions are identical in all hitherto an alyzed mammalian fructose-1,6-bisphosphatase isoenzyme genes. Transcription al start sites were found to be located 97 and 95 bp before the start codon in the human gene and 35 bp before the start codon in the mouse homolog. A comparison of the 5'-flanking sequences of the two genes revealed a 56% ho mology up to human bp -607 before the first transcriptional start point, wh ile upstream of this region we found no similarity. The data presented in t his paper provide a basis for further studies of the mechanism of expressio n regulation and the elucidation of the physiological role of the enzyme. ( C) 2000 Elsevier Science B.V. All rights reserved.