Gametic and pleiotropic defects in mouse fetuses with Hertwig's macrocytic anemia.

Pleiotropic effects on germ cell number, hematologic status, and body size are described in 12- to 15-day WBB6F1 normal (+/-) and defective (an/an) mouse fetuses, with special emphasis on gametogenesis. Differences between genotypes were apparent by Day 12. At 12 days, normal testes contained many germ cells and frequent normal mitoses, and the number of germ cells increased rapidly from Day 12 to Day 15. By contrast, 12-day an/an testes contained fewer germ cells, frequently degenerating, and many abnormal mitoses. Their number of germ cells decreased rapidly, so that almost none persisted to Day 15. Normal ovaries contained many germ cells, with much normal mitosis on Day 12 and 13, followed by meioses, but the smaller an/an ovaries contained few germ cells, with little mitosis, some meiosis, and very much degeneration. The erythrocyte counts of both normal and anemic fetuses increased approximately fourfold between 12 and 15 days, but at comparable ages, total counts were always lower in an/an fetuses than in normal littermates. At all ages, Hertwig's anemic (an/an) fetuses were somewhat smaller than their normal littermates. Although both W/Wv and Sl/Sld mice also show macrocytic anemia and germ cell failure, the great difference in etiology of their germ cell defects indicates that an/an gene action must be qualitatively different from that in either W/Wv or Sl/Sld mice.