SEQUENCE AND TISSUE-DEPENDENT RNA EXPRESSION OF MOUSE FAD-LINKED GLYCEROL-3-PHOSPHATE DEHYDROGENASE

A 2432-bp cDNA for mouse FAD-linked glycerol-3-phosphate dehydrogenase , a nuclear-encoded enzyme associated with the inner mitochondrial mem brane, was isolated from a Lambda ZAP phage library generated from bro wn adipocyte mRNA The amino acid sequence was 95 and 93% homologous to the rat and human enzymes. PvuII and SacI polymorphisms between Mus s pretus and C57BL/6J were used to map the mouse FAD-linked glycerol-3-p hosphate dehydrogenase gene (Gdm1) to chromosome 2, 33 cM from the cen tromere. Northern blot analysis showed that brown adipose tissue predo minantly expressed a 6.5-kb mRNA with lower expression of 4.5- and 2.4 -kb forms, whereas brain and pancreatic islets almost exclusively expr essed a 6.5-kb transcript, muscle expressed a 4.5-kb transcript, and t estis expressed a 2.4-kb RNA form. Analysis of poly(A)(+) RNA hom brow n adipose tissue suggested that all RNA forms are polyadenylated. Amon g the tissues examined, FAD-linked glycerol-3-phosphate dehydrogenase protein levels and enzyme activity were highest in brown adipose tissu e, and a consistent correlation between protein levels and enzyme acti vity in all tissues was observed. RNA levels corresponded to protein l evels in all tissues except testis, where high levels of 2.4-kb mRNA a nd relatively low protein were expressed. Exposing mice to cold temper atures induced the 6.5-kb mRNA and enzyme activity only in brown adipo se tissue, suggesting a role for thermogenesis in this tissue. Althoug h the molecular basis for the formation of the 6.5- and 4.5-kb mRNA's is not known, data suggest that the regulation of FAD-linked glycerol- 3-phosphate dehydrogenase is complex and tissue-specific. (C) 1996 Aca demic Press, Inc.