| RRC ID |
21896
|
| Author |
Sanders RD, Sefton JM, Moberg KH, Fridovich-Keil JL.
|
| Title |
UDP-galactose 4' epimerase (GALE) is essential for development of Drosophila melanogaster.
|
| Journal |
Dis Model Mech
|
| Abstract |
UDP-galactose 4' epimerase (GALE) catalyzes the interconversion of UDP-galactose and UDP-glucose in the final step of the Leloir pathway; human GALE (hGALE) also interconverts UDP-N-acetylgalactosamine and UDP-N-acetylglucosamine. GALE therefore plays key roles in the metabolism of dietary galactose, in the production of endogenous galactose, and in maintaining the ratios of key substrates for glycoprotein and glycolipid biosynthesis. Partial impairment of hGALE results in the potentially lethal disorder epimerase-deficiency galactosemia. We report here the generation and initial characterization of a first whole-animal model of GALE deficiency using the fruit fly Drosophila melanogaster. Our results confirm that GALE function is essential in developing animals; Drosophila lacking GALE die as embryos but are rescued by the expression of a human GALE transgene. Larvae in which GALE has been conditionally knocked down die within days of GALE loss. Conditional knockdown and transgene expression studies further demonstrate that GALE expression in the gut primordium and Malpighian tubules is both necessary and sufficient for survival. Finally, like patients with generalized epimerase deficiency galactosemia, Drosophila with partial GALE loss survive in the absence of galactose but succumb in development if exposed to dietary galactose. These data establish the utility of the fly model of GALE deficiency and set the stage for future studies to define the mechanism(s) and modifiers of outcome in epimerase deficiency galactosemia.
|
| Volume |
3(9-10)
|
| Pages |
628-38
|
| Published |
2010-1-1
|
| DOI |
10.1242/dmm.005058
|
| PII |
dmm.005058
|
| PMID |
20519568
|
| PMC |
PMC2931539
|
| MeSH |
Alleles
Animals
Drosophila melanogaster / drug effects
Drosophila melanogaster / embryology*
Drosophila melanogaster / enzymology*
Embryo, Nonmammalian / drug effects
Embryo, Nonmammalian / enzymology
Embryo, Nonmammalian / pathology
Galactose / metabolism
Galactose / pharmacology
Galactosephosphates / metabolism
Gastrointestinal Tract / drug effects
Gastrointestinal Tract / enzymology
Humans
Malpighian Tubules / drug effects
Malpighian Tubules / enzymology
Metabolic Networks and Pathways / drug effects
Mutation / genetics
UDPglucose 4-Epimerase / metabolism*
|
| IF |
4.651
|
| Times Cited |
21
|
|
WOS Category
|
PATHOLOGY
CELL BIOLOGY
|
| Resource |
| Drosophila |
12030R-2 |
