Homozygous carnitine palmitoyltransferase 1b (muscle isoform) deficiency is lethal in the mouse

Shaonin Ji, Yun You, Janos Kerner, Charles L. Hoppel, Trenton R. Schoeb, Wallace S H Chick, Doug A. Hamm, J. Daniel Sharer, Philip A. Wood

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67 Scopus citations


Carnitine palmitoyltransferase-1 (CPT-1) catalyzes the rate-limiting step of mitochondrial β-oxidation of long chain fatty acids (LCFA), the most abundant fatty acids in mammalian membranes and in energy metabolism. Human deficiency of the muscle isoform CPT-1b is poorly understood. In the current study, embryos with a homozygous knockout of Cpt-1b were lost before embryonic day 9.5-11.5. Also, while there were normal percentages of CPT-1b+/- pups born from both male and female CPT-1b+/- mice crossed with wild-type mates, the number of CPT-1b+/- pups from CPT-1b+/- breeding pairs was under-represented (63% of the expected number). Northern blot analysis demonstrated ∼50% Cpt-1b mRNA expression in brown adipose tissue (BAT), heart and skeletal muscles in the CPT-1b+/- male mice. Consistent with tissue-specific expression of Cpt-1b mRNA in muscle but not liver, CPT-1+/- mice had ∼60% CPT-1 activity in skeletal muscle and no change in total liver CPT-1 activity. CPT-1b+/- mice had normal fasting blood glucose concentration. Consistent with expression of CPT-1b in BAT and muscle, ∼7% CPT-1b+/- mice (n = 30) developed fatal hypothermia following a 3 h cold challenge, while none of the CPT-1b+/+ mice (n = 30) did. With a prolonged cold challenge (6 h), significantly more CPT-1b+/- mice developed fatal hypothermia (52% CPT-1b+/- mice vs. 21% CPT-1b+/+ mice), with increased frequency in females of both genotypes (67% female vs. 38% male CPT-1b+/- mice, and 33% female vs. 8% male CPT-1b+/+ mice). Therefore, lethality of homozygous CPT-1b deficiency in the mice is consistent with paucity of human cases.

Original languageEnglish (US)
Pages (from-to)314-322
Number of pages9
JournalMolecular Genetics and Metabolism
Issue number3
StatePublished - Mar 2008

Bibliographical note

Funding Information:
We thank Drs. Greg Cox and Roger Sher for providing some of the founder mice, Drs. Ada Elgavish and Jianfang Hu for helpful discussion and valuable assistance in biostatistics. This publication was made possible by Grant No. R01-RR02599 from the National Center for Research Resource (NCRR), a component of the National Institutes of Health (NIH). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of NCRR or NIH. This work was also supported by the Office of Biological and Environmental Research, U.S. Department of Energy (Y.Y.), under contract DE-AC05-00OR22725 with UT-Battelle, LLC.


  • Carnitine palmitoyltransferase-1b
  • Cold intolerance
  • Gestational lethality


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