Study of New Roles in AMP Metabolism by Using Gene Modified Animals

点击翻译按钮获取中文摘要

AMP deaminase (AMPD) catalyzes AMP to IMP and is thought to play an important role in purine metabolism, though detailed function of AMPD in vivo has not been understood. Therefore, we established gene knock-out mice for each AMPD gene to elucidate in vivo function of three AMPD genes. Furthermore, we tried to produce model mice for combined AMPD deficiency by mating these AMPD knock-out mice. AMPD2 knockout mice showed muscle specific deficiency of AMPD and increased AMP/ATP ratio in skeletal muscle as well as more phophorylation of AMP-activated kinase in muscle. AMPD2 knockout mice exhibited proteinuria along with decreased AMPD activity in kidney and liver. Also, they showed increased AMP and increase of phophorylated AMPK and ACC in liver. AMPD3 knockout mice exhibited decreased AMPD acitivity in red cells and heart, and they showed increased ATP in red cells without other prominent phenotype. About combined AMPD deficiency, AMPD2/AMPD3 double deficient mice were found to die before 3 weeks after birth, though AMPD1/AMPD2 double deficient mice as well as AMPD1/AMPD3 double deficient mice were established. These studies revealed the functional relevance of AMPD in kidney as well as liver.