title: Y chromosome-linked B and NK cell deficiency in mice.
abstract: There are no primary immunodeficiency diseases linked to the Y chromosome, because the Y chromosome does not contain any vital genes. We have established a novel mouse strain in which all males lack B and NK cells and have Peyer's patch defects. By 10 wk of age, 100% of the males had evident immunodeficiencies. Mating these immunodeficient males with wild-type females on two different genetic backgrounds for several generations demonstrated that the immunodeficiency is linked to the Y chromosome and is inherited in a Mendelian fashion. Although multicolor fluorescence in situ hybridization analysis showed that the Y chromosome in the mutant male mice was one third shorter than that in wild-type males, exome sequencing did not identify any significant gene mutations. The precise molecular mechanisms are still unknown. Bone marrow chimeric analyses demonstrated that an intrinsic abnormality in bone marrow hematopoietic cells causes the B and NK cell defects. Interestingly, fetal liver cells transplanted from the mutant male mice reconstituted B and NK cells in lymphocyte-deficient Il2rg(-/-) recipient mice, whereas adult bone marrow transplants did not. Transducing the EBF gene, a master transcription factor for B cell development, into mutant hematopoietic progenitor cells rescued B cell but not NK cell development both in vitro and in vivo. These Y chromosome-linked immunodeficient mice, which have preferential B and NK cell defects, may be a useful model of lymphocyte development.
authors.affiliation: Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
authors.forename: Shu-lan
authors.initials: SL
authors.lastname: Sun
authors.forename: Satoshi
authors.initials: S
authors.lastname: Horino
authors.forename: Ari
authors.initials: A
authors.lastname: Itoh-Nakadai
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kawabe
authors.forename: Atsuko
authors.initials: A
authors.lastname: Asao
authors.forename: Takeshi
authors.initials: T
authors.lastname: Takahashi
authors.forename: Takanori
authors.initials: T
authors.lastname: So
authors.forename: Ryo
authors.initials: R
authors.lastname: Funayama
authors.forename: Motonari
authors.initials: M
authors.lastname: Kondo
authors.forename: Hirotomo
authors.initials: H
authors.lastname: Saitsu
authors.forename: Naomichi
authors.initials: N
authors.lastname: Matsumoto
authors.forename: Keiko
authors.initials: K
authors.lastname: Nakayama
authors.forename: Naoto
authors.initials: N
authors.lastname: Ishii
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D004195:Disease Models, Animal; D005434:Flow Cytometry; D050173:Genes, Y-Linked / Q000235:genetics / Q000276:immunology; D050174:Genetic Diseases, Y-Linked / Q000235:genetics* / Q000276:immunology*; D007153:Immunologic Deficiency Syndromes / Q000235:genetics* / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction