A transgenic mouse model for non-immune hydrops fetalis induced by the NS1 gene of human parvovirus B19.
Human parvovirus B19 (B19) infection during pregnancy is associated with the adverse foetal outcome known as non-immune hydrops fetalis (NIHF). Although B19 is known to infect erythroid-lineage cells in vivo as well as in vitro, the mechanism leading to the occurrence of NIHF is not clear. To investigate the possible involvement of the B19 non-structural protein NS1 in NIHF, three independent lines of transgenic mice were generated that expressed NS1 under the control of the Cre-loxP system and the GATA1 promoter. Two of the three lines expressed NS1 in erythroid-lineage cells. Most of the transgenic mice died at the embryonic stage, some of which developed hydropic changes caused by severe anaemia at embryonic day 15.5 (E15.5). Histological examination of embryos at E15.5 showed significantly fewer erythropoietic islands in the liver parenchyma, whereas their hearts showed no abnormal signs, such as cardiomegaly and apoptotic cells. The NS1-transgenic mouse lines established here provide an animal model for human NIHF and suggest that NS1 plays a crucial role in the adverse outcome associated with intrauterine B19 infection in humans.
Chisaka
Hiroshi
H
Department of Microbiology and Immunology1 and Department of Obstetrics and Gynecology2, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
Morita
Eiji
E
Department of Microbiology and Immunology1 and Department of Obstetrics and Gynecology2, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
Murata
Kazuko
K
CREST Program of the Japan Science and Technology Corporation, Sendai 980-8575, Japan3.|Department of Microbiology and Immunology1 and Department of Obstetrics and Gynecology2, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
Ishii
Naoto
N
Department of Microbiology and Immunology1 and Department of Obstetrics and Gynecology2, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
Yaegashi
Nobuo
N
Department of Microbiology and Immunology1 and Department of Obstetrics and Gynecology2, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
Okamura
Kunihiro
K
Department of Microbiology and Immunology1 and Department of Obstetrics and Gynecology2, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
Sugamura
Kazuo
K
Department of Microbiology and Immunology1 and Department of Obstetrics and Gynecology2, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004622:Embryo, Mammalian / Q000473:pathology; D015672:Erythroid Precursor Cells; D050981:Erythroid-Specific DNA-Binding Factors; D005260:Female; D005313:Fetal Death; D050982:GATA1 Transcription Factor; D015160:Hydrops Fetalis / Q000196:embryology / Q000209:etiology* / Q000473:pathology; D019426:Integrases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D010322:Parvoviridae Infections / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D016732:Parvovirus B19, Human / Q000235:genetics* / Q000378:metabolism; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000473:pathology / Q000503:physiopathology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured; D017361:Viral Nonstructural Proteins / Q000235:genetics* / Q000378:metabolism; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism
D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; C494689:Gata1 protein, mouse; C106202:NS1 protein, parvovirus; D014157:Transcription Factors; D017361:Viral Nonstructural Proteins; D014764:Viral Proteins; C045073:Cre recombinase; D019426:Integrases