Analysis Tools
hematopoietic system
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• homozygotes exhibit normal circulating numbers of mature red and white blood cells and platelets relative to wild-type controls
• no significant differences in thymus cellularity or thymocyte subsets are observed
• B-cell subsets in the bone marrow, spleen and peritoneum are normal
• both spleens and thymuses are of normal size
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• at 6-8 weeks of age, homozygotes display a severely reduced thymic T-cell proliferation in response to concanavalin A and allogeneic stimulation relative to wild-type controls
• peripheral T-cell responses remain normal
• however, when lethally irradiated wild-type mice are reconstituted with mutant bone marrow or spleen cells, normal thymic T-cell stimulation is observed, suggesting a defect in the hematopoietic microenvironment
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• granulocyte-macrophage (GM-colony forming capacity) progenitors are reduced by 73% in spleen but are less affected in the bone marrow
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• committed erythroid (BFU-E) progenitors are reduced by 85% in spleen but are less affected in the bone marrow
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• pluripotent hematopoietic stem cells (CFU-S) are reduced by 88% in spleen and by 59% in the bone marrow
• however, total nucleated cell numbers and the subset of hematopoietic progenitors defined by markers Sca+Thyl+Lin- in spleen and bone marrow are normal
• injection of mutant spleen and bone marrow cells promotes long-term survival of lethally irradiated wild-type mice, indicating that mutant stem cells remain pluripotent
• the diminished CFU-S pool can be restored by exogenous LIF (103 IU)
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immune system
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• at 6-8 weeks of age, homozygotes display a severely reduced thymic T-cell proliferation in response to concanavalin A and allogeneic stimulation relative to wild-type controls
• peripheral T-cell responses remain normal
• however, when lethally irradiated wild-type mice are reconstituted with mutant bone marrow or spleen cells, normal thymic T-cell stimulation is observed, suggesting a defect in the hematopoietic microenvironment
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growth/size/body
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• homozygotes are overtly normal but somewhat smaller than wild-type controls
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reproductive system
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• no uterine expression of the heparin-binding EGF-like growth factor (HB-EGF) is detected in the luminal epithelium at the site of blastocyst apposition at the anticipated time prior to the attachment reaction on day 4 or even on the morning of day 5 of pregnancy, unlike in wild-type controls
• however, HB-EGF expression in brain or in the luminal epithelium on day 1 of pregnancy is equivalent to that in wild-type controls
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• epiregulin, which is normally expressed in the luminal epithelium and underlying stroma adjacent to the implanting blastocyst at the time of the attachment reaction on day 4 and then on day 5, is not induced on day 5 of pregnancy in mutant uteri
• uterine expression of prostaglandin-endoperoxide synthase 2 (Ptgs2) is normally present in the luminal epithelium but absent in underlying stromal cells surrounding the blastocyst during the attachment reaction on day 5 of pregnancy, unlike in wild-type controls
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• blastocysts fail to implant partly due to loss or aberrant expression of specific members of the EGF family of growth factors in mutant uteri before and during the expected time of implantation, although EGF receptor family members are properly expressed
• however, uterine cell-specific proliferation and differentation, responsiveness to ovarian steroids, and expression of angiogenic factors remain normal during the preimplantation period in mutant uteri
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• amphiregulin, which is normally expressed in the luminal and glandular epithelia of wild-type uteri, is undetectable in mutant uteri on day 4 of pregnancy, suggesting that uterine preparation is impaired despite normal plasma progesterone levels
• however, amphiregulin is induced in ovariectomized mutant uteri after progesterone (P4) treatment, though at reduced levels
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• female homozygotes are infertile due to uterine defects that affect embryo implantation
(J:63668)
• female, but not male, homozygotes are sterile
(J:77410)
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cellular
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• at 6-8 weeks of age, homozygotes display a severely reduced thymic T-cell proliferation in response to concanavalin A and allogeneic stimulation relative to wild-type controls
• peripheral T-cell responses remain normal
• however, when lethally irradiated wild-type mice are reconstituted with mutant bone marrow or spleen cells, normal thymic T-cell stimulation is observed, suggesting a defect in the hematopoietic microenvironment
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