RRC ID 77783
Author Miyasaka Y, Okuda K, Miura I, Motegi H, Wakana S, Ohno T.
Title A novel ENU-induced Cpox mutation causes microcytic hypochromic anemia in mice.
Journal Exp Anim
Abstract Mouse models of red blood cell abnormalities are important for understanding the underlying molecular mechanisms of human erythrocytic diseases. DBA.B6-Mha (Microcytic hypochromic anemia) congenic mice were generated from the cross between N-ethyl-N-nitrosourea (ENU)-mutagenized male C57BL/6J and female DBA/2J mice as part of the RIKEN large-scale ENU mutagenesis project. The mice were established by backcrossing with DBA/2J mice for more than 20 generations. These mice showed autosomal-dominant microcytic hypochromic anemia with decreased mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) levels and increased red blood cell distribution width (RDW) and plasma ferritin levels. Linkage analysis indicated that the Mha locus was located within an interval of approximately 1.95-Mb between D16Nut1 (58.35 Mb) and D16Mit185 (60.30 Mb) on mouse chromosome 16. Mutation analysis revealed that DBA.B6-Mha mice had a point mutation (c.921-2A>G) at the acceptor site of intron 4 in the coproporphyrinogen oxidase (Cpox) gene, a heme-synthesizing gene. RT-PCR revealed that the Cpox mRNA in DBA.B6-Mha mice caused splicing errors. Our results suggest that microcytic hypochromic anemia in DBA.B6-Mha mice is owing to impaired heme synthesis caused by splice mutations in Cpox. Therefore, the DBA.B6-Mha mice may be used to elucidate the molecular mechanisms underlying microcytic hypochromic anemia caused by mutations in Cpox. Although low MCV levels are known to confer malarial resistance to the host, there were no marked changes in the susceptibility of DBA.B6-Mha mice to rodent malarial (Plasmodium yoelii 17XL) infection.
Volume 71(4)
Pages 433-441
Published 2022-11-10
DOI 10.1538/expanim.22-0032
PMID 35527013
PMC PMC9671764
MeSH Anemia, Hypochromic* / chemically induced Anemia, Hypochromic* / genetics Animals Coproporphyrinogen Oxidase* / genetics Female Heme Male Mice Mice, Inbred C57BL Mice, Inbred DBA Mutation
IF 1.574
Mice RBRCGSC0129