Skip to main content
NCBI home page
Wiley - PMC COVID-19 Collection logoLink to Wiley - PMC COVID-19 Collection
. 2005 Jun 3;47(6):884–892. doi: 10.1002/ajmg.1320470616

Pathologic characterization of short‐chain acyl‐CoA dehydrogenase deficiency in BALB/cByJ mice

Dawna L Armstrong 1, Michael L Masiowski 1, Philip A Wood 2,✉
PMCID: PMC7159464  PMID: 8279487

Abstract

BALB/cByJ mice have a deficiency of short‐chain acyl‐CoA dehydrogenase (SCAD) and are a useful model for studying the inborn errors of fatty acid metabolism which affect humans. Patients with some of these disorders present with hypoglycemia, hyperamonemia, and microvesicular fatty change of hepatocytes. In the present study we examined pathogen‐free, SCAD deficient BALB/cByJ mice and control BALB/cBy mice for biochemical and tissue changes following fasting or salicylate challenge. We observed mitochondrial swelling and microvesicular fatty changes in hepatocytes in mutant mice, especially severe following a fast. However, fasting did not alter their blood ammonia and there was no apparent clinical disease. Similarly, salicylates did not produce disease in the BALB/cByJ mice. We did detect in mice an alternative pathway for salicylate metabolism, by‐passing glycine conjugation which is the principal metabolic pathway in humans. © 1993 Wiley‐Liss, Inc.

Keywords: short‐chain acyl‐CoA dehydrogenase, BALB/cByJ, Reyelike syndrome, morphology, biochemistry, salicylate metabolism

References

  1. Bougneres PF, Rocchiccioli F, Kolvaa S, Hadchouel M, Lalau‐Keraly J, Chaussain J‐L, Wadman SK, Gregersen N (1985): Medium‐chain acyl‐CoA dehydrogenase deficiency in two siblings with a Reye‐like syndrome. J Pediatr 106: 918–921. [DOI] [PubMed] [Google Scholar]
  2. Brownstein DG, Johnson EA, Smith AL (1984): Spontaneous Reye's‐like syndrome in BALB/cByJ mice. Lab Invest 51: 386–395. [PubMed] [Google Scholar]
  3. Chang LW, Gilbert EF, Tanner W, Moffat HL (1973): Reye syndrome: Light and electron microscopic studies. Arch Pathol Lab Med 96: 127–132. [PubMed] [Google Scholar]
  4. Daugherty CC, Gartside PS, Heubi JE, Saalfeld K, Synder J (1987): A morphometric study of Reye's syndrome: Correlation of reduced mitochondrial numbers and increased mitochondrial size with clinical manifestations. Am J Pathol 129: 313–326. [PMC free article] [PubMed] [Google Scholar]
  5. Dobowitz V, Brooke MH (1973): Histological and Histochemical stains and reactions In Walter JW. (ed): “Muscle Biopsy: A Modern Approach, Volume 2 Major Problems in Neurology.” Philadelphia: W.B. Saunders Co., pp 19–40. [Google Scholar]
  6. Goodman AGG, Goodman LS, Gilman A (1980): “The Pharmacological Basis of Therapeutics.” New York: Macmillan, pp 694–695. [Google Scholar]
  7. Greene CL, Blitzer MG, Sharpira E (1988): Inborn errors of metabolism and Reye syndrome: differential diagnosis. J Pediatr 113: 156–159. [DOI] [PubMed] [Google Scholar]
  8. Hurwitz ES (1989): Reye's syndrome. Epidemiol Rev 11: 249–253. [DOI] [PubMed] [Google Scholar]
  9. Iancu TC, Mason WH, Neustein HB (1977): Ultrastructural abnormalities of liver cells in Reye's syndrome. Hum Pathol 8: 421–431. [DOI] [PubMed] [Google Scholar]
  10. Nuzum CT, Snodgrass PJ (1976): Multiple assays of the 5 urea cycle enzymes in human liver homogenates In Grisoli S, Baguena R, Mayor F. (eds): “The Urea Cycle.” New York: John Wiley and Sons, pp. 325–349. [Google Scholar]
  11. Partin JC, Schubert WK, Partin JS (1971): Mitochondrial ultrastructure in Reye's syndrome (encephalopathy and fatty degeneration of the viscera). N Engl J Med 285: 1339–1343. [DOI] [PubMed] [Google Scholar]
  12. Partin JC, Partin JS, Schubert WK, McLaurin RL (1975): Brain ultrastructure in Reye's syndrome (encephalopathy and fatty alteration of the viscera). J Neuropathol Exp Neurol 34: 425–444. [DOI] [PubMed] [Google Scholar]
  13. Partin JS, McAdams AJ, Partin JC, Schubert WK, McLaurin RL (1978): Brain ultrastructure in Reye's disease. II. Acute injury and recovery processes in three children. J Neuropathol Exp Neurol 37: 796–819. [PubMed] [Google Scholar]
  14. Reye RDK, Morgan G, Baral J (1963): Encephalopathy and fatty degeneration of the viscera: a disease entity in childhood. Lancet 2: 749–752. [DOI] [PubMed] [Google Scholar]
  15. Roe CR, Millington DS, Maltby DA, Kinnebrew P (1986): Recognition of medium‐chain acyl‐CoA dehydrogenase deficiency in asymptomatic siblings of children dying of sudden infant death or Reye‐like syndromes. J Pediatr 108: 13–18. [DOI] [PubMed] [Google Scholar]
  16. Schubert WK, Partin JC, Partin JS (1972): Encephalopathy and fatty liver (Reye's syndrome) In Proper H, Schaffner F. (eds): “Progress in Liver Disease.” New York: Grune and Stratton, pp. 489–510. [PubMed] [Google Scholar]
  17. Treem WR, Witzleben CA, Piccoli DA, Stanley CA, Hale DE, Coates PM, Watkins JB (1986): Medium‐chain and long‐chain acyl‐CoA dehydrogenase deficiency:clinical, pathologic and ultrastructural differentiation from Reye's syndrome. Hepatology 5: 1270–1278. [DOI] [PubMed] [Google Scholar]
  18. Wood PA, Armstrong D, Sauls D, Davisson MT (1988): Screening mutant mice for inborn errors of metabolism. Lab Anim Sci 38: 15–19. [PubMed] [Google Scholar]
  19. Wood PA, Amendt BA, Rhead WJ, Millington DS, Inone F, Armstrong D (1989): Short‐chain acylcoenzyme: a dehydrogenase deficiency in mice. Pediatr Res 25: 38–43. [DOI] [PubMed] [Google Scholar]

Articles from American Journal of Medical Genetics are provided here courtesy of Wiley

RESOURCES