Serotonin Deficiency and Prolonged Bleeding in Beige Mice 1

Abstract

Summary

Beige mice have been observed to bleed excessively from small wounds. Platelets obtained from these mice were deficient in adenine nucleotides and serotonin and in vivo uptake of labeled serotonin was impaired. Heterozygotes of beige and C57BL/6 mice have adenine nucleotide and serotonin levels comparable to control and do not manifest a bleeding tendency, consistent with the recessive mode of inheritance of the beige mouse syndrome. Morphologic confirmation of the observed biochemical defects was obtained by the demonstration that serotonin storage organelles were not observed in electron photomicrographs of beige mouse platelets. The demonstration that small doses of serotonin were effective in reversing the bleeding tendency in beige mice suggested a causal role for defective storage and release of endogenous serotonin as the basis for the bleeding tendency, acting either independently or synergistically with impaired release of adenine nucleotides.

The author wishes to express gratitude to Drs. D.J. Prieur, G. A. Padgett and T. T. Odell for their advice and encouragement during the preparation of this manuscript. The excellent technical assistance of Ms. J. W. Hall and C. S. King were also appreciated.