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.
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.
Authors: K Eggan; H Akutsu; J Loring; L Jackson-Grusby; M Klemm; W M Rideout; R Yanagimachi; R Jaenisch Journal: Proc Natl Acad Sci U S A Date: 2001-05-01 Impact factor: 11.205
Authors: Ana Claudia Zenclussen; Katrin Gerlof; Maria Laura Zenclussen; André Sollwedel; Annarosa Zambon Bertoja; Thomas Ritter; Katja Kotsch; Joachim Leber; Hans-Dieter Volk Journal: Am J Pathol Date: 2005-03 Impact factor: 4.307
Authors: Guillermina Girardi; Dmitry Yarilin; Joshua M Thurman; V Michael Holers; Jane E Salmon Journal: J Exp Med Date: 2006-08-21 Impact factor: 14.307