High incidence of uterine inversion in mast cell-deficient osteopetrotic mutant mice of mi/mi genotype

H. Yokoi, H. Nakayama, K. Horie, M. Fukumoto, K. Fujita, Y. Kaneko, M. Iwai, S. Natsuyama, H. Kanzaki, K. J. Mori, J. Fujita

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12 Citations (Scopus)

Abstract

Mutations at either W or mi (microphthalmia) loci in the mouse can lead to a deficiency in melanocytes and mast cells. In addition, W mutants can be anemic and sterile, whereas mi mice are osteopetrotic because of a monocyte/macrophage/osteoclast defect. Since c-kit receptor tyrosine kinase is the gene product of the W locus and mi mutation has been suggested to affect the transduction of signals from the c-kit and c-fms receptors, we here examined the effect of mi mutation on fertility. Testes and ovaries from mi/mi mice were histologically normal, and the pattern of c-kit protein expression was not different from that of +/+ mice. Homozygous mutant crosses (mi/mi x mi/mi) were fertile, but inversion of the uterus occurred in 86% of the deliveries. In some cases, the placenta was found still attached to the inverted uterus after delivery. Decidual cells were present and expressed c- kit protein normally in the placenta of mi/mi mice. The inversion was also observed in mi/mi females mated to +/+ males. No uterine inversion was noted when +/mi females were crossed with mi/mi or +/mi males, suggesting that the genotype of the mother but not of the father or fetus is important for the pathogenesis. The numbers and body weights of mi/mi newborns were less than those of +/mi littermates. Mast cells were absent, but c-kit-positive cells were present, in the uterine muscle layers of pregnant mi/mi mice. These results indicate that the normal mi gene product is necessary, directly or indirectly, for the normal growth and delivery of the fetus, and that the mi/mi mouse will be useful as an animal model of the uterine inversion.

Original languageEnglish
Pages (from-to)1034-1039
Number of pages6
JournalBiology of Reproduction
Volume50
Issue number5
DOIs
Publication statusPublished - 1994

ASJC Scopus subject areas

  • Reproductive Medicine
  • Cell Biology

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