CRISPR/Cas9-mediated knockout of CD47 causes hemolytic anemia with splenomegaly in C57BL/6 mice.
10.5625/lar.2018.34.4.302
- Author:
Joo Il KIM
1
;
Jin Sung PARK
;
Jina KWAK
;
Hyun Jin LIM
;
Soo Kyung RYU
;
Euna KWON
;
Kang Min HAN
;
Ki Taek NAM
;
Han Woong LEE
;
Byeong Cheol KANG
Author Information
1. Graduate School of Translational Medicine, Seoul National University College of Medicine, Seoul, Korea. bckang@snu.ac.kr
- Publication Type:Original Article
- Keywords:
CRISPR/Cas9;
CD47;
hemolytic anemia;
splenomegaly
- MeSH:
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
- From:Laboratory Animal Research
2018;34(4):302-310
- CountryRepublic of Korea
- Language:English
-
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.
