- Whole animal genetic model for Galactosemia.
- Fly model can be used to test efficacy of novel therapeutic interventions.
- Genetic system enables screening for suppressors and/or genetic modifiers
- First whole-animal genetic model to study GALT and GALE function.
- Only model that mimics acute and long-term outcomes seen in human
Emory researchers have created a novel fly model for galactosemia which has
distinct advantages over previously used in vitro cell culture systems
and in vivo mouse models as it recapitulates significant aspects of the
human disease. Galactosemias are a family of potentially lethal disorders that
result from impaired metabolism of galactose, affecting around one in 60,000
live births. Classic galactosemia results from a loss of galactose-1-phosphate
uridylyltransferase (GALT), and generalized epimerase-deficiency galactosemia
results from a loss of UDP-galactose 4'-epimerase (GALE). Despite more than 50
years of investigation, the mechanisms underlying the pathophysiology of
galactosemia remain unclear.
Emory investigators recently created a whole-animal genetic model to study
this lethal disorder. In their GALT deficient D. melanogaster
model, the absence of dGALT results in a galactose-dependent
lethality of developing larvae, an outcome that is rescued by
transgenic expression of human GALT. The researchers have further
demonstrated that loss of dGALE is lethal even in the absence of
dietary galactose exposure and that providing increasing amounts of dietary
galactose exacerbates this phenotype by hastening death. In contrast, complete
loss of dGALT is not lethal unless the animals are exposed to
galactose. This fly model stands in welcome contrast to the GALT
knockout mouse which remained healthy despite a complete lack of GALT,
even when challenged with large quantities of dietary galactose.
In vivo proof of principle has been demonstrated in the fly model of