Lab Anim Res.  2018 Dec;34(4):302-310. 10.5625/lar.2018.34.4.302.

CRISPR/Cas9-mediated knockout of CD47 causes hemolytic anemia with splenomegaly in C57BL/6 mice

Affiliations
  • 1Graduate School of Translational Medicine, Seoul National University College of Medicine, Seoul, Korea. bckang@snu.ac.kr
  • 2Department of Experimental Animal Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea.
  • 3Department of Pathology, Dongguk University Ilsan Hospital, Goyang, Korea.
  • 4College of Medicine Severance Biomedical Science Institute, Yonsei University, Seoul, Korea.
  • 5Department of Biochemistry, Yonsei University, Seoul, Korea.
  • 6Biomedical Center for Animal Resource and Development, Seoul National University, College of Medicine, Seoul, Korea.
  • 7Designed Animal and Transplantation Research Institute, Institute of Green Bio Science Technology, Seoul National University, Pyeongchang-gun, Korea.

Abstract

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.

Keyword

CRISPR/Cas9; CD47; hemolytic anemia; splenomegaly

MeSH Terms

Adolescent
Anemia
Anemia, Hemolytic*
Animals
Erythrocyte Indices
Erythrocytes
Female
Humans
Leukocytes
Macrophages
Male
Mice*
Parturition
Phagocytosis
Phenotype
Puberty
Reticulocyte Count
Sex Ratio
Spleen
Splenomegaly*
T-Lymphocytes
Thymus Gland
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