|
|
 Previous Article | Table of Contents | Next Article 
Blood, Vol. 94 No. 9 (November 1), 1999:
pp. 2945-2954
Increased Sensitivity to Complement and a Decreased Red Blood Cell Life
Span in Mice Mosaic for a Nonfunctional Piga Gene
G. Tremml,
C. Dominguez,
V. Rosti,
Z. Zhang,
P.P. Pandolfi,
P. Keller, and
M. Bessler
From the Department of Human Genetics, Memorial Sloan-Kettering
Cancer Center, New York, NY; and the Division of
Hematology, Department of Medicine, Washington University School
of Medicine, St Louis, MO.
The gene PIGA encodes one of the protein subunits of the
 1-6-N acetylglucosaminyltransferase complex, which catalyses an early step in the biosynthesis of glycosyl phosphatidylinositol (GPI)
anchors. PIGA is somatically mutated in blood cells from patients with paroxysmal nocturnal hemoglobinuria (PNH), leading to
deficiency of GPI-linked proteins on the cell surface. To investigate in detail how inactivating mutations of the PIGA gene affect
hematopoiesis, we generated a mouse line, in which
loxP-mediated excision of part of exon 2 occurs on the
expression of Cre. After crossbreeding with EIIa-cre transgenic
mice, recombination occurs early in embryonic life. Mice that are
mosaics for the recombined Piga gene are viable and lack
GPI-linked proteins on a proportion of circulating blood cells. This
resembles the coexistence of normal cells and PNH cells in patients
with an established PNH clone. PIGA( ) blood cells in mosaic mice
have biologic features characteristic of those classically seen in
patients with PNH, including an increased sensitivity toward complement
mediated lysis and a decreased life span in circulation. However,
during the 12-month follow-up, the PIGA() cell population did not
increase, clearly showing that a Piga gene mutation is not
sufficient to cause the human disease, PNH.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
M. Bessler and J. Hiken
The Pathophysiology of Disease in Patients with Paroxysmal Nocturnal Hemoglobinuria
Hematology,
January 1, 2008;
2008(1):
104 - 110.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Gargiulo, S. Lastraioli, G. Cerruti, M. Serra, F. Loiacono, S. Zupo, L. Luzzatto, and R. Notaro
Highly homologous T-cell receptor beta sequences support a common target for autoreactive T cells in most patients with paroxysmal nocturnal hemoglobinuria
Blood,
June 1, 2007;
109(11):
5036 - 5042.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. D. Friend, D. D. Shah, C. Deppong, J. Lin, T. L. Bricker, T. I. Juehne, C. M. Rose, and J. M. Green
A dose-dependent requirement for the proline motif of CD28 in cellular and humoral immunity revealed by a targeted knockin mutant
J. Exp. Med.,
September 4, 2006;
203(9):
2121 - 2133.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Hill, S. H. Ridley, D. Esser, R. G. Oldroyd, M. J. Cullen, P. Kareclas, S. Gallagher, G. P. Smith, S. J. Richards, J. White, et al.
Protection of erythrocytes from human complement-mediated lysis by membrane-targeted recombinant soluble CD59: a new approach to PNH therapy
Blood,
March 1, 2006;
107(5):
2131 - 2137.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Hanaoka, T. Kawaguchi, K. Horikawa, S. Nagakura, H. Mitsuya, and H. Nakakuma
Immunoselection by natural killer cells of PIGA mutant cells missing stress-inducible ULBP
Blood,
February 1, 2006;
107(3):
1184 - 1191.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Baalasubramanian, C. L. Harris, R. M. Donev, M. Mizuno, N. Omidvar, W.-C. Song, and B. P. Morgan
CD59a Is the Primary Regulator of Membrane Attack Complex Assembly in the Mouse
J. Immunol.,
September 15, 2004;
173(6):
3684 - 3692.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Jasinski, P. Pantazopoulos, R. P. Rother, N. van Rooijen, W.-C. Song, H. Molina, and M. Bessler
A novel mechanism of complement-independent clearance of red cells deficient in glycosyl phosphatidylinositol-linked proteins
Blood,
April 1, 2004;
103(7):
2827 - 2834.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Takahashi, J. P. McCoy Jr, C. Carvallo, C. Rivera, T. Igarashi, R. Srinivasan, N. S. Young, and R. W. Childs
In vitro and in vivo evidence of PNH cell sensitivity to immune attack after nonmyeloablative allogeneic hematopoietic cell transplantation
Blood,
February 15, 2004;
103(4):
1383 - 1390.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Leneuve, S. Colnot, G. Hamard, F. Francis, M. Niwa-Kawakita, M. Giovannini, and M. Holzenberger
Cre-mediated germline mosaicism: a new transgenic mouse for the selective removal of residual markers from tri-lox conditional alleles
Nucleic Acids Res.,
March 1, 2003;
31(5):
e21 - e21.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Kulkarni and M. Bessler
The effect of GPI-anchor deficiency on apoptosis in mice carrying a Piga gene mutation in hematopoietic cells
J. Leukoc. Biol.,
December 1, 2002;
72(6):
1228 - 1233.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Murakami, H. Kosaka, Y. Maeda, J.-i. Nishimura, N. Inoue, K. Ohishi, M. Okabe, J. Takeda, and T. Kinoshita
Inefficient response of T lymphocytes to glycosylphosphatidylinositol anchor-negative cells: implications for paroxysmal nocturnal hemoglobinuria
Blood,
December 1, 2002;
100(12):
4116 - 4122.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Nagakura, S. Ishihara, D. E. Dunn, J.-i. Nishimura, T. Kawaguchi, K. Horikawa, M. Hidaka, T. Kagimoto, N. Eto, H. Mitsuya, et al.
Decreased susceptibility of leukemic cells with PIG-A mutation to natural killer cells in vitro
Blood,
July 18, 2002;
100(3):
1031 - 1037.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R J Johnson and P Hillmen
Paroxysmal nocturnal haemoglobinuria: Nature's gene therapy?
Mol. Pathol.,
June 1, 2002;
55(3):
145 - 152.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Jasinski, P. Keller, Y. Fujiwara, S. H. Orkin, and M. Bessler
GATA1-Cre mediates Piga gene inactivation in the erythroid/megakaryocytic lineage and leads to circulating red cells with a partial deficiency in glycosyl phosphatidylinositol-linked proteins (paroxysmal nocturnal hemoglobinuria type II cells)
Blood,
October 1, 2001;
98(7):
2248 - 2255.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Keller, J. L. Payne, G. Tremml, P. A. Greer, M. Gaboli, P. P. Pandolfi, and M. Bessler
FES-Cre Targets Phosphatidylinositol Glycan Class A (PIGA) Inactivation to Hematopoietic Stem Cells in the Bone Marrow
J. Exp. Med.,
August 27, 2001;
194(5):
581 - 590.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. S. Holt, M. Botto, A. E. Bygrave, S. M. Hanna, M. J. Walport, and B. P. Morgan
Targeted deletion of the CD59 gene causes spontaneous intravascular hemolysis and hemoglobinuria
Blood,
July 15, 2001;
98(2):
442 - 449.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Holzenberger, C. Lenzner, P. Leneuve, R. Zaoui, G. Hamard, S. Vaulont, and Y. L. Bouc
Cre-mediated germline mosaicism: a method allowing rapid generation of several alleles of a target gene
Nucleic Acids Res.,
November 1, 2000;
28(21):
e92 - e92.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Karadimitris, J. S. Manavalan, H. T. Thaler, R. Notaro, D. J. Araten, K. Nafa, I. A.G. Roberts, M. E. Weksler, and L. Luzzatto
Abnormal T-cell repertoire is consistent with immune process underlying the pathogenesis of paroxysmal nocturnal hemoglobinuria
Blood,
October 1, 2000;
96(7):
2613 - 2620.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Luzzatto
Paroxysmal Murine Hemoglobinuria(?): A Model for Human PNH
Blood,
November 1, 1999;
94(9):
2941 - 2944.
[Full Text]
[PDF]
|
|
|
|
|
