EDTP Loss of Function Impairs Longevity and Reproduction

Abstract

This study presents a comprehensive genetic characterization of DJ694, a viable GAL4 enhancer-trap allele of the age-regulated gene EDTP. EDTP transcript levels are reduced in DJ694, and homozygous flies exhibit reduced reproduction and shortened lifespan in both sexes. The fertility and longevity phenotypes are recessive and can be fully rescued by three independent UAS-EDTP insertions. Expression of UAS-EDTP into animals with wildtype phenotypes does not affect female fertility or lifespan. DJ694 has a jumpy behaviour but it is not detected by a locomotion assay. Like its human homolog, Muscle-specific Inositol Phosphatase (MIP, also known as MTMR14), EDTP is mainly expressed in adult muscles. The structure of the muscle, myofibril, and sarcomere appears normal in homozygous DJ694. DJ694 females have morphologically normal ovaries, implicating a functional rather than structural impairment. We demonstrate that EDTP is required during both development and adulthood to support normal fertility, with expression restricted to either stage alone being insufficient. Although it has been reported that EDTP can influence the accumulation of polyglutamine aggregates, we did not find evidence in its native tissue. Ectopic expression in the eye reduces the amount of aggregates but EDTP overexpression in muscles has no detectable effect on the accumulation or toxicity of two different kinds of polyglutamine aggregates.