Anemia and perinatal death result from loss of the murine ecotropic retrovirus receptor mCAT-1.
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| Abstract |
The mCAT-1 gene encodes a basic amino acid transporter that also acts as the receptor for murine ecotropic leukemia viruses. Targeted mutagenesis in embryonic stem cells has been used to introduce a germ-line null mutation into this gene. This mutation removes a domain critical for virus binding and inactivates amino acid transport activity. Homozygous mutant pups generated from these cells were approximately 25% smaller than normal littermates, very anemic, and died on the day of birth. Peripheral blood from homozygotes contained 50% fewer red blood cells, reduced hemoglobin levels, and showed a pronounced normoblastosis. Histological analyses of bone marrow, spleen, and liver showed a decrease in both erythroid progenitors and mature red blood cells. Mutant fetal liver cells behaved normally in in vitro hematopoietic colony-forming assays but generated an anemia when transplanted into irradiated C.B.-17 SCID mice. Furthermore, reconstitution of the white cell compartment of SCID mice by mutant fetal liver cells was less complete than that observed with a mixed population of wild-type and heterozygous fetal liver cells. Primary embryo fibroblasts from mutant mice were completely resistant to ecotropic retrovirus infection. Thus, mCAT-1 not only appears to be the sole receptor for a group of murine ecotropic retroviruses associated with hematological disease but also plays a critical role in both hematopoiesis and growth control during mouse development.
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| Authors | C P Perkins, V Mar, J R Shutter, J del Castillo, D M Danilenko, E S Medlock, I L Ponting, M Graham, K L Stark, Y Zuo, J M Cunningham, R A Bosselman |
| Journal | Genes & development (Genes Dev) Vol. 11 Issue 7 Pg. 914-25 (Apr 01 1997) ISSN: 0890-9369 [Print] United States |
| PMID | 9106662 (Publication Type: Journal Article) |
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