Pancreatic function in carboxyl-ester lipase knockout mice

Pancreatology. 2010;10(4):467-76. doi: 10.1159/000266284. Epub 2010 Aug 19.


Background/aims: CEL-MODY is a monogenic form of diabetes and exocrine pancreatic insufficiency due to mutations in the carboxyl-ester lipase (CEL) gene. We aimed to investigate endocrine and exocrine pancreatic function in CEL knockout mice (CELKO).

Methods: A knockout mouse model with global targeted deletion of CEL was investigated physiologically and histopathologically, and compared to littermate control CEL+/+ mice at 7 and 12 months on normal chow and high-fat diets (HFD), i.e. 42 and 60% fat by calories.

Results: CELKO+/+ and -/- mice showed normal growth and development and normal glucose metabolism on a chow diet. Female CEL-/- mice on 60% HFD, on the other hand, had increased random blood glucose compared to littermate controls (p = 0.02), and this was accompanied by a reduction in glucose tolerance that did not reach statistical significance. In these mice there was also islet hyperplasia, however, α- and β-islet cells appeared morphologically normal and pancreatic exocrine function was also normal.

Conclusion: Although we observed mild glucose intolerance in female mice with whole-body knockout of CEL, the full phenotype of human CEL-MODY was not reproduced, suggesting that the pathogenic mechanisms involved are more complex than a simple loss of CEL function. and IAP.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Blood Glucose / genetics
  • Disease Models, Animal
  • Female
  • Glucagon-Secreting Cells / cytology
  • Glucagon-Secreting Cells / metabolism
  • Glucose Tolerance Test
  • Insulin-Secreting Cells / cytology
  • Insulin-Secreting Cells / metabolism
  • Intestinal Absorption / genetics
  • Islets of Langerhans / cytology
  • Islets of Langerhans / enzymology*
  • Lipase / physiology*
  • Longevity / genetics
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Pancreas, Exocrine / cytology
  • Pancreas, Exocrine / enzymology*
  • Weight Gain / genetics


  • Blood Glucose
  • Lipase