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.
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Drenth J P, Prieur A M. Occurrence of arthritis in hyper-immunoglobulinaemia D. Ann Rheum Dis, 1993, 52: 765–766
Drenth J P, Boom B W, Toonstra J, et al. Cutaneous manifestations and histologic findings in the hyperimmunoglobulinemia D syndrome. International Hyper IgD Study Group. Arch Dermatol, 1994, 130: 59–65
Drenth J P, Haagsma C J, van der Meer J W. Hyperimmuno-globulinemia D and periodic fever syndrome. The clinical spectrum in a series of 50 patients. International Hyper-IgD Study Group. Medicine (Baltimore), 1994, 73: 133–144
van der Meer J W, Vossen J M, Radl J, et al. Hyperimmuno-globulinaemia D and periodic fever: a new syndrome. Lancet, 1984, 1: 1087–1090
Naruto T, Nakagishi Y, Mori M, et al. Hyper-IgD syndrome with novel mutation in a Japanese girl. Mod Rheumatol, 2009, 19: 96–99
Yoshimura K, Wakiguchi H. Hyperimmunoglobulinemia D syndrome successfully treated with a corticosteroid. Pediatr Int, 2002, 44: 326–327
Klasen I S, Goertz J H, van de Wiel G A, et al. Hyper-immuno-globulin A in the hyperimmunoglobulinemia D syndrome. Clin Diagn Lab Immun, 2001, 8: 58–61
Frenkel J, Rijkers G T, Mandey S H, et al. Lack of isoprenoid products raises ex vivo interleukin-1beta secretion in hyperimmuno-globulinemia D and periodic fever syndrome. Arthrit Rheumat, 2002, 46: 2794–2803
Drenth J P, Cuisset L, Grateau G, et al. Mutations in the gene encoding mevalonate kinase cause hyper-IgD and periodic fever syndrome. International Hyper-IgD Study Group. Nat Genet, 1999, 22: 178–181
Simon A, Cuisset L, Vincent M F, et al. Molecular analysis of the mevalonate kinase gene in a cohort of patients with the hyper-igd and periodic fever syndrome: its application as a diagnostic tool. Ann Intern Med, 2001, 135: 338–343
Houten S M, van Woerden C S, Wijburg F A, et al. Carrier frequency of the V377I (1129G>A) MVK mutation, associated with Hyper-IgD and periodic fever syndrome, in the Netherlands. Eur J Hum Genet, 2003, 11: 196–200
Aringer M. Periodic fever syndromes—a clinical overview. Acta Med Austriaca, 2004, 31: 8–12
Drenth J P, van der Meer J W. Hereditary periodic fever. N Engl J Med, 2001, 345: 1748–1757
Hager E J, Tse H M, Piganelli J D, et al. Deletion of a single mevalonate kinase (Mvk) allele yields a murine model of hyper-IgD syndrome. J Inherit Metab Dis, 2007, 30: 888–895
Ammouri W, Cuisset L, Rouaghe S, et al. Diagnostic value of serum immunoglobulinaemia D level in patients with a clinical suspicion of hyper IgD syndrome. Rheumatology, 2007, 46: 1597–1600
Dikeacou T C, van Joost T, Cormane R H. The recruitment of inflammatory cells using the skin-window technique. Arch Dermatol Res, 1979, 265: 1–7
Chen K, Cerutti A. New insights into the enigma of immunoglobulin D. Immunol Rev, 2010, 237: 160–179
Vladutiu A O. Immunoglobulin D: properties, measurement, and clinical relevance. Clin Diagn Lab Immun, 2000, 7: 131–140
Gorski K, Carneiro M, Schibler U. Tissue-specific in vitro transcription from the mouse albumin promoter. Cell, 1986, 47: 767–776
Herbomel P, Rollier A, Tronche F, et al. The rat albumin promoter is composed of six distinct positive elements within 130 nucleotides. Mol Cell Biol, 1989, 9: 4750–4758
Heard J M, Herbomel P, Ott M O, et al. Determinants of rat albumin promoter tissue specificity analyzed by an improved transient expression system. Mol Cell Biol, 1987, 7: 2425–2434
Kraus C L, Culican S M. Nummular keratopathy in a patient with Hyper-IgD Syndrome. Pediatr Rheumatol Online J, 2009, 7: 14
Sornsakrin M, Wenner K, Ganschow R. B cell cytopenia in two brothers with hyper-IgD and periodic fever syndrome. Eur J Pediatr, 2009, 168: 825–831
Attout H, Guez S, Ranaivo I, et al. A patient with hyper-IgD syndrome responding to simvastatin treatment. Eur J Intern Med, 2008, 19: e82–83
Coban E, Terzioglu E. A patient with hyper-IgD syndrome in Antalya, Turkey. Clin Rheumatol, 2004, 23: 177–178
Tronche F, Rollier A, Bach I, et al. The rat albumin promoter: cooperation with upstream elements is required when binding of APF/HNF1 to the proximal element is partially impaired by mutation or bacterial methylation. Mol Cell Biol, 1989, 9: 4759–4766
Zhang D E, Ge X, Rabek J P, et al. Functional analysis of the trans-acting factor binding sites of the mouse alpha-fetoprotein proximal promoter by site-directed mutagenesis. J Biol Chem, 1991, 266: 21179–21185
Izban M G, Papaconstantinou J. Cell-specific expression of mouse albumin promoter—evidence for cell-specific DNA elements within the proximal promoter region and cis-acting DNA elements upstream of −160. J Biol Chem, 1989, 264: 9171–9179
Pinkert C A, Ornitz D M, Brinster R L, et al. An albumin enhancer located 10-kb upstream functions along with its promoter to direct efficient, liver-specific expression in transgenic mice. Gene Dev, 1987, 1: 268–276
Hu J M, Camper S A, Tilghman S M, et al. Functional analyses of albumin expression in a series of hepatocyte cell lines and in primary hepatocytes. Cell Growth Differ, 1992, 3: 577–588
Clark A J, Cowper A, Wallace R, et al. Rescuing transgene expression by co-integration. Biotechnology (NY), 1992, 10: 1450–1454
Tang B, Yu S, Zheng M, et al. High level expression of a functional human/mouse chimeric anti-CD20 monoclonal antibody in milk of transgenic mice. Transgenic Res, 2008, 17: 727–732
Enjuanes L, Sola I, Castilla J, et al. Transgenic mice secreting coronavirus neutralizing antibodies into the milk. J Virology, 1998, 72: 3762–3772
Fine J M, Rivat C, Lambin P, et al. Monoclonal IgD. A comparative study of 60 sera with IgD “M” component. Biomedicine, 1974, 21: 119–125
Fibbe W E, Jansen J. Prognostic factors in IgD myeloma: a study of 21 cases. Scand J Haematol, 1984, 33: 471–475
Rowe D S, Hug K, Forni L, et al. Immunoglobulin-D as a lymphocyte receptor. J Exp Med, 1973, 138: 965–972
Ligthart G J, Schuit H R, Hijmans W. Subpopulations of mononuclear cells in ageing: expansion of the null cell compartment and decrease in the number of T and B cells in human blood. Immunology, 1985, 55: 15–21
Chen K, Xu W, Wilson M, et al. Immunoglobulin D enhances immune surveillance by activating antimicrobial, proinflammatory and B cell-stimulating programs in basophils. Nat Immunol, 2009, 10: 889–898
Obici L, Manno C, Muda A O, et al. First report of systemic reactive (AA) amyloidosis in a patient with the hyperimmunoglobulinemia D with periodic fever syndrome. Arthritis Rheum, 2004, 50: 2966–2969
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Wang, P., Wei, Z., Yan, B. et al. Establishment of a transgenic mouse model with liver-specific expression of secretory immunoglobulin D. Sci. China Life Sci. 55, 219–227 (2012). https://doi.org/10.1007/s11427-012-4301-3
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DOI: https://doi.org/10.1007/s11427-012-4301-3