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  • 标题:CRISPR/Cas9-mediated knockout of CD47 causes hemolytic anemia with splenomegaly in C57BL/6 mice
  • 本地全文:下载
  • 作者:Joo-Il Kim ; Jin-Sung Park ; Jina Kwak
  • 期刊名称:Laboratory Animal Research
  • 印刷版ISSN:1738-6055
  • 电子版ISSN:2233-7660
  • 出版年度:2018
  • 卷号:34
  • 期号:4
  • 页码:302-310
  • DOI:10.5625/lar.2018.34.4.302
  • 语种:English
  • 出版社:BioMed Central Ltd.
  • 摘要:CD47 (integrin-associated protein), a multi-spanning transmembrane protein expressed in all cells including red blood cells (RBCs) and leukocytes, interacts with signal regulatory protein α (SIRPα) on macrophages and thereby inhibits phagocytosis of RBCs. Recently, we generated a novel C57BL/6J CD47 knockout (CD47-/- hereafter) mouse line by employing a CRISPR/Cas9 system at Center for Mouse Models of Human Disease, and here report their hematological phenotypes. On monitoring their birth and development, CD47-/- mice were born viable with a natural male-to-female sex ratio and normally developed from birth through puberty to adulthood without noticeable changes in growth, food/water intake compared to their age and sex-matched wild-type littermates up to 26 weeks. Hematological analysis revealed a mild but significant reduction of RBC counts and hemoglobin in 16 week-old male CD47-/- mice which were aggravated at the age of 26 weeks with increased reticulocyte counts and mean corpuscular volume (MCV), suggesting hemolytic anemia. Interestingly, anemia in female CD47-/- mice became evident at 26 weeks, but splenomegaly was identified in both genders of CD47-/- mice from the age of 16 weeks, consistent with development of hemolytic anemia. Additionally, helper and cytotoxic T cell populations were considerably reduced in the spleen, but not in thymus, of CD47-/- mice, suggesting a crucial role of CD47 in proliferation of T cells. Collectively, these findings indicate that our CD47-/- mice have progressive hemolytic anemia and splenic depletion of mature T cell populations and therefore may be useful as an in vivo model to study the function of CD47.
  • 关键词:CRISPR/Cas9;CD47;hemolytic anemia;splenomegaly
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