{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T22:55:04Z","timestamp":1781304904352,"version":"3.54.1"},"reference-count":36,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2011,2,25]],"date-time":"2011-02-25T00:00:00Z","timestamp":1298592000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cardiovasc electrophysiol"],"published-print":{"date-parts":[[2011,8]]},"abstract":"<jats:p> <jats:bold>Transgenic Murine Models of CHB. <jats:italic>Introduction:<\/jats:italic> Congenital heart block (CHB) is a passively acquired autoimmune disease considered to be due to the transfer of maternal autoantibodies, anti\u2010SSA\/Ro \u2013SSB\/La, to the fetus resulting in atrioventricular (AV) block and sinus bradycardia. We previously established a murine model for CHB where pups born to immunized wild\u2010type (WT) mothers exhibited electrocardiographic abnormalities similar to those seen in CHB and demonstrated inhibition of L\u2010type Ca channels (LTCCs) by maternal antibodies. Here, we hypothesize that overexpression of LTCC should rescue, whereas knockout of LTCC should worsen the electrocardiographic abnormalities in mice.<\/jats:bold> <\/jats:p><jats:p> <jats:bold>\n            <jats:italic>Methods and Results:<\/jats:italic> Transgenic (TG) mice were immunized with SSA\/Ro and SSB\/La antigens. Pups born to immunized WT mothers had significantly greater sinus bradycardia and AV block compared to pups from nonimmunized WT. TG pups overexpressing LTCC had significantly less sinus bradycardia and AV block compared to their non\u2010TG littermates and to pups born to immunized WT mothers. All LTCC knockout pups born to immunized mothers had sinus bradycardia, advanced degree of AV block, and decreased fetal parity. No sinus bradycardia or AV block were manifested in pups from control nonimmunized WT mothers. IgG from mothers with CHB children, but not normal IgG, completely inhibited intracellular Ca transient ([Ca]<jats:sub>i<\/jats:sub>T) amplitude.<\/jats:bold> <\/jats:p><jats:p> <jats:bold>\n            <jats:italic>Conclusions:<\/jats:italic> Cardiac\u2010specific overexpression of LTCC significantly reduced the incidence of AV block and sinus bradycardia in pups exposed to anti\u2010SSA\/Ro \u2010SSB\/La autoantibodies, whereas exposure of LTCC knockout pups to these autoantibodies significantly worsened the electrocardiographic abnormalities. These findings support the hypothesis that maternal antibodies inhibit LTCC and [Ca]<jats:sub>i<\/jats:sub>T thus contributing to the development of CHB. Altogether, the results are relevant to the development of novel therapies for CHB<\/jats:bold>. <jats:italic>(J Cardiovasc Electrophysiol, Vol. 22, pp. 922\u2010930, August 2011)<\/jats:italic><\/jats:p>","DOI":"10.1111\/j.1540-8167.2011.02032.x","type":"journal-article","created":{"date-parts":[[2011,2,26]],"date-time":"2011-02-26T16:03:04Z","timestamp":1298736184000},"page":"922-930","source":"Crossref","is-referenced-by-count":39,"title":["Rescue and Worsening of Congenital Heart Block\u2010Associated Electrocardiographic Abnormalities in Two Transgenic Mice"],"prefix":"10.1111","volume":"22","author":[{"given":"EDDY","family":"KARNABI","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"YONGXIA","family":"QU","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"SALVATORE","family":"MANCARELLA","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MOHAMED","family":"BOUTJDIR","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,2,25]]},"reference":[{"key":"e_1_2_10_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/B978-012433901-9\/50020-X"},{"key":"e_1_2_10_3_2","first-page":"1058","volume-title":"Neonatal Lupus. 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