Journal
JOURNAL OF CLINICAL INVESTIGATION
Volume 107, Issue 11, Pages 1403-1409Publisher
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI12590
Keywords
-
Categories
Funding
- NIADDK NIH HHS [AM-20407] Funding Source: Medline
- NIDDK NIH HHS [DK-02574] Funding Source: Medline
Ask authors/readers for more resources
Mitochondrial trifunctional protein (MTP) is a hetero-octamer of four a and four P subunits that catalyzes the final three steps of mitochondrial long chain fatty acid P-oxidation. Human MTP deficiency causes Reye-like syndrome, cardiomyopathy, or sudden unexpected death. We used gene targeting to generate an MTP a subunit null allele and to produce mice that lack MTP ex and P subunits. The Mtpa(-/-) fetuses accumulate long chain fatty acid metabolites and have low birth weight compared with the Mtpa(+/-) and Mtpa(+/+) littermates, Mtpa(-/-) mice suffer neonatal hypoglycemia and sudden death 6-36 hours after birth, Analysis of the histopathological changes in the Mtpa(-/-) PUPS revealed rapid development of hepatic steatosis after birth and, later, significant necrosis and acute degeneration of the cardiac and diaphragmatic myocytes. This mouse model documents that intact mitochondrial long chain fatty acid oxidation is essential for fetal development and for survival after birth. Deficiency of MTP causes fetal growth retardation, neonatal hypoglycemia, and sudden death.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available