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CRISPR/Cas9-mediated knockout ofCD47causes hemolytic anemia with splenomegaly in C57BL/6 mice
- Source :
- Laboratory Animal Research, Laboratory Animal Research, Vol 34, Iss 4, Pp 302-310 (2018)
- Publication Year :
- 2018
- Publisher :
- Springer Science and Business Media LLC, 2018.
-
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.
- Subjects :
- 0301 basic medicine
C57BL/6
Hemolytic anemia
medicine.medical_specialty
Anemia
Spleen
03 medical and health sciences
Reticulocyte
Internal medicine
medicine
Cytotoxic T cell
CD47
lcsh:QH301-705.5
CRISPR/Cas9
Mean corpuscular volume
hemolytic anemia
lcsh:R5-920
splenomegaly
medicine.diagnostic_test
biology
biology.organism_classification
medicine.disease
030104 developmental biology
medicine.anatomical_structure
Endocrinology
lcsh:Biology (General)
Original Article
Hemoglobin
lcsh:Medicine (General)
Subjects
Details
- ISSN :
- 22337660 and 17386055
- Volume :
- 34
- Database :
- OpenAIRE
- Journal :
- Laboratory Animal Research
- Accession number :
- edsair.doi.dedup.....53641ea977501e61f060b14a73389be9