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Published on: May 21, 2015
Syngeneic immune-dependent abortions in mice suggest paternal alloantigen-independent mechanisms
Jean A Kundert1, Amy L Sealey, Yan Li
1Animal Resources Center, Montana State University, Bozeman, MT 59718, USA.
Problem:
Recurrent immune-associated miscarriages in humans are thought to result from maternal immune responses to paternal alloantigens. We investigated the role of paternal alloantigens in a mouse model of immune-dependent abortion.
Method Of Study:
Sib-crosses of C57Bl/6J (haplotype b/b) mice heterozygous for a targeted hypomorphic allele of the tbp gene (tbp(deltaN/+)) resulted in selective mid-gestational abortion of 88% of the tbp(deltaN/deltaN) fetuses. In dams lacking mature lymphocytes (rag1-/-), nearly all tbp(deltaN/deltaN) fetuses survived to birth, indicating abortions were immune-dependent. Allogeneic pregnancies bearing tbp(deltaN/deltaN) fetuses were established by either hybridizing the paternal lineage to BALB/cJ (haplotype d/d) and mating hybrid tbp(deltaN/+) sires to haplotype b/b tbp(deltaN/+) C57Bl/6J dams, or by transfer of haplotype b/b zygotes from tbp(deltaN/+)x tbp(deltaN/+) matings into pseudopregnant wild-type CByD2F1/J dams (haplotype d/d).
Results:
Neither hemizygous paternal allogeneic loci nor homozygous allogeneic loci, including a haplotype-mismatched major histocompatibility complex (MHC), increased abortion frequencies.
Conclusion:
Results suggested that mechanisms for maternal tolerance of paternal alloantigens, including mismatched MHC antigens, were intact in these pregnancies, yet maternal immune-dependent paternal antigen-independent abortion of mutants occurred. These data indicate that, in some cases of immune-mediated abortions, the presence of paternal alloantigens can be coincidental and superfluous to the compromising rejection response.
