title: Establishment of a transgenic mouse model with liver-specific expression of secretory immunoglobulin D.
abstract: Mutation of mevalonate kinase (MVK) is thought to account for most cases of hyperimmunoglobulinemia D syndrome (HIDS) with recurrent fever. However, its mechanism and the relationship between elevated serum immunoglobulin D (IgD) and the clinical features of HIDS are unclear. In this study, we generated by fusion PCR a vector to express high levels of chimeric secretory IgD (csIgD) specifically in the liver. We then generated seven founder lines of transgenic mice by co-microinjection, and verified them using genomic PCR and Southern blotting. We detected the expression of csIgD by reverse transcription PCR, quantitative PCR, western blotting, and enzyme-linked immunosorbent assays. We demonstrated that csIgD could be specifically and stably expressed in the liver. We used flow cytometry to show that overexpression of csIgD in the bone marrow and spleen cells had no effect on B cell development. Morphologic and anatomical observation of the transgenic mice revealed skin damage, hepatosplenomegaly, and nephromegaly in some transgenic mice; in these mice, pathological sections showed high levels of cell necrosis and protein-like sediments in the liver, spleen, and kidney. We demonstrated that the genomic insertion sites of the transgenes did not disrupt the MVK gene on mouse chromosome 5. This transgenic mouse will be useful to explore the pathogenesis of HIDS.
authors.affiliation: College of Biological Sciences, China Agricultural University, State Key Laboratories for Agrobiotechnology, Beijing 100193, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.forename: ZhiGuo
authors.initials: Z
authors.lastname: Wei
authors.forename: BoWen
authors.initials: B
authors.lastname: Yan
authors.forename: Tan
authors.initials: T
authors.lastname: Huang
authors.forename: KeMian
authors.initials: K
authors.lastname: Gou
authors.forename: YunPing
authors.initials: Y
authors.lastname: Dai
authors.forename: Min
authors.initials: M
authors.lastname: Zheng
authors.forename: MeiLi
authors.initials: M
authors.lastname: Wang
authors.forename: XueQian
authors.initials: X
authors.lastname: Cheng
authors.forename: XiFeng
authors.initials: X
authors.lastname: Wang
authors.forename: Chen
authors.initials: C
authors.lastname: Xu
authors.forename: Yi
authors.initials: Y
authors.lastname: Sun
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology; D015139:Blotting, Southern; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005786:Gene Expression Regulation; D005822:Genetic Vectors; D007072:Immunoglobulin D / Q000096:biosynthesis* / Q000737:chemistry*; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008957:Models, Genetic; D009154:Mutation; D016133:Polymerase Chain Reaction / Q000379:methods; D013154:Spleen / Q000378:metabolism; D019076:Transgenes
chemical_list: D007072:Immunoglobulin D