TISSUE-SPECIFIC RESCUE SUGGESTS THAT PLACENTAL ADENOSINE-DEAMINASE IS IMPORTANT FOR FETAL DEVELOPMENT IN MICE

被引:50
作者
BLACKBURN, MR
WAKAMIYA, M
CASKEY, CT
KELLEMS, RE
机构
[1] BAYLOR COLL MED,VERNA & MARRS MCLEAN DEPT BIOCHEM,HOUSTON,TX 77030
[2] BAYLOR COLL MED,DEPT MOLEC & HUMAN GENET,HOUSTON,TX 77030
关键词
D O I
10.1074/jbc.270.41.23891
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Adenosine deaminase (ADA, EC 3.5.4.4) is an essential enzyme of purine metabolism that is expressed at very high levels in the murine placenta where it accounts for over 95% of the ADA present at the fetal gestation site. We have recently shown that ADA-deficient fetuses, which also lack ADA in their adjoining placentas, die during late fetal development in association with profound purine metabolic disturbances and hepatocellular impairment. We have now investigated the potential importance of placental ADA by genetically restoring the enzyme to placentas of ADA-deficient fetuses. This genetic engineering strategy corrected most of the purine metabolic disturbances, prevented serious fetal liver damage, and rescued the fetuses from perinatal lethality. Our findings suggest that placental ADA is important for murine fetal development and illustrate a general strategy for the tissue specific correction of phenotypes associated with null mutations in mice.
引用
收藏
页码:23891 / 23894
页数:4
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