mortality/aging
• intercrosses of heterozygotes produce viable homozygous offspring at the expected Mendelian ratios
• however, embryos developing in homozygous mutant mothers appear necrotic at >7.5 dpc, with rare instances (<1%) of intact embryos detected at 9.5 dpc, and no live embryos found after 10.5 dpc
• notably, 2.5 dpc mutant embryos survive normally when transferred in foster uteri, whereas wild-type embryos fail to do so in uteri of mutant mice
|
reproductive system
N |
• virgin female homozygotes display normal estrous cyclicity and mating behavior, as well as histologically normal ovaries, oviducts, vagina and uterus
|
• the decidua basalis is entirely absent, being replaced by multiple layers of trophoblast giant cells
|
• in a few cases, the decidua capsularis is present but significantly thinner
|
• at 4.5 dpc, uteri of pregnant homozygotes display a reduced secondary decidual response to the implanting blastocyst
• at 5.5-7.5 dpc, mutant deciduae are significantly smaller, displaying hemorrhage in the uterine lumen, disruption of the antimesometrium, and overgrowth of giant trophoblast cells in the mesometrial portion of the deciduum
• notably, pseudopregnant homozygotes show reduced deciduoma formation in response to an artificial (oil) stimulus, albeit with partial preservation of mesometrial decidual tissue
|
• at 4.5-7.5 dpc, homozygotes display a normal number of implantation sites relative to wild-type mice
• however, mutants show reduced capillary permeability and blood flow in the uterine vascular bed at the site of blastocyst apposition
|
embryo
• pregnant homozygotes exhibit a significantly increased number of secondary trophoblast giant cells in the mutant decidua
|
• the decidua basalis is entirely absent, being replaced by multiple layers of trophoblast giant cells
|
• in a few cases, the decidua capsularis is present but significantly thinner
|
• in most cases, embryos surviving in 9.5 dpc mutant uteri contain fibrinoid material and inflammatory cells in the space normally occupied by the placenta
• in a few cases, embryos surviving in 9.5 dpc mutant uteri display fetal components of the chorioallantoic placenta; however, the decidua basalis is entirely absent, being replaced by multiple layers of trophoblast giant cells, while the decidua capsularis is present but significantly thinner
|
• at 4.5 dpc, uteri of pregnant homozygotes display a reduced secondary decidual response to the implanting blastocyst
• at 5.5-7.5 dpc, mutant deciduae are significantly smaller, displaying hemorrhage in the uterine lumen, disruption of the antimesometrium, and overgrowth of giant trophoblast cells in the mesometrial portion of the deciduum
• notably, pseudopregnant homozygotes show reduced deciduoma formation in response to an artificial (oil) stimulus, albeit with partial preservation of mesometrial decidual tissue
|