Hematological defects in the oc/oc mouse, a model of infantile malignant osteopetrosis
Identifieur interne : 00B950 ( Main/Merge ); précédent : 00B949; suivant : 00B951Hematological defects in the oc/oc mouse, a model of infantile malignant osteopetrosis
Auteurs : C. Blin-Wakkach [France] ; A. Wakkach [France] ; P. M. Sexton [Australie] ; N. Rochet [France] ; G. F. Carle [France]Source :
- Leukemia [ 0887-6924 ] ; 2004.
Descripteurs français
- Pascal (Inist)
- Wicri :
- topic : Enfant.
English descriptors
- KwdEn :
Abstract
Infantile malignant osteopetrosis (IMO) is a rare and lethal disease characterized by an absence of bone resorption due to inactive OCLs. Affected patients display an increased bone mass and hematological defects. The osteopetrotic oc/oc mouse displays a bone phenotype similar to the one observed in IMO patients, and the same gene, Tcirg1, is mutated in this model and in the majority of these patients. Therefore, we explored in oc/oc mice the consequences of the perturbed bone microenvironment on hematopoiesis. We show that the myelomonocytic differentiation is increased, leading to an elevated number of OCLs and dendritic cells. B lymphopoiesis is blocked at the pro-B stage in the bone marrow of oc/oc mouse, leading to a low mature B-cell number. T-cell activation is also affected, with a reduction of IFNγ secretion by splenic CD4 T cells. These alterations are associated with a low IL-7 expression in bone marrow. All these data indicate that the lack of bone resorption in oc/oc mice has important consequences in both myelopoiesis and lymphopoiesis, leading to a form of immunodeficiency. The oc/oc mouse is therefore an appropriate model to understand the hematological defects described in IMO patients, and to derive new therapeutic strategies.
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Pascal:04-0483813Le document en format XML
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Blin-Wakkach</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>GPM FRE2720, CNRS/UNSA, Faculté de Médecine, av de Valombrose</s1><s2>Nice</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Provence-Alpes-Côte d'Azur</region><region type="old region">Provence-Alpes-Côte d'Azur</region><settlement type="city">Nice</settlement></placeName></affiliation></author><author><name sortKey="Wakkach, A" sort="Wakkach, A" uniqKey="Wakkach A" first="A." last="Wakkach">A. Wakkach</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>GPM FRE2720, CNRS/UNSA, Faculté de Médecine, av de Valombrose</s1><s2>Nice</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Provence-Alpes-Côte d'Azur</region><region type="old region">Provence-Alpes-Côte d'Azur</region><settlement type="city">Nice</settlement></placeName></affiliation></author><author><name sortKey="Sexton, P M" sort="Sexton, P M" uniqKey="Sexton P" first="P. M." last="Sexton">P. M. Sexton</name><affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Howard Florey Institute, The University of Melbourne</s1><s2>Victoria</s2><s3>AUS</s3><sZ>3 aut.</sZ></inist:fA14><country>Australie</country><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName><orgName type="university">Université de Melbourne</orgName></affiliation></author><author><name sortKey="Rochet, N" sort="Rochet, N" uniqKey="Rochet N" first="N." last="Rochet">N. Rochet</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>GPM FRE2720, CNRS/UNSA, Faculté de Médecine, av de Valombrose</s1><s2>Nice</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Provence-Alpes-Côte d'Azur</region><region type="old region">Provence-Alpes-Côte d'Azur</region><settlement type="city">Nice</settlement></placeName></affiliation></author><author><name sortKey="Carle, G F" sort="Carle, G F" uniqKey="Carle G" first="G. F." last="Carle">G. F. Carle</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>GPM FRE2720, CNRS/UNSA, Faculté de Médecine, av de Valombrose</s1><s2>Nice</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Provence-Alpes-Côte d'Azur</region><region type="old region">Provence-Alpes-Côte d'Azur</region><settlement type="city">Nice</settlement></placeName></affiliation></author></analytic><series><title level="j" type="main">Leukemia</title><title level="j" type="abbreviated">Leukemia</title><idno type="ISSN">0887-6924</idno><imprint><date when="2004">2004</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Leukemia</title><title level="j" type="abbreviated">Leukemia</title><idno type="ISSN">0887-6924</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animal model</term><term>Child</term><term>Hematology</term><term>Hematopoiesis</term><term>Lymphopoiesis</term><term>Malignant tumor</term><term>Mouse</term><term>Osteoclast</term><term>Osteopetrosis</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Tumeur maligne</term><term>Modèle animal</term><term>Souris</term><term>Ostéopétrose</term><term>Enfant</term><term>Hématopoïèse</term><term>Lymphopoïèse</term><term>Ostéoclaste</term><term>Hématologie</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Enfant</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Infantile malignant osteopetrosis (IMO) is a rare and lethal disease characterized by an absence of bone resorption due to inactive OCLs. Affected patients display an increased bone mass and hematological defects. The osteopetrotic oc/oc mouse displays a bone phenotype similar to the one observed in IMO patients, and the same gene, Tcirg1, is mutated in this model and in the majority of these patients. Therefore, we explored in oc/oc mice the consequences of the perturbed bone microenvironment on hematopoiesis. We show that the myelomonocytic differentiation is increased, leading to an elevated number of OCLs and dendritic cells. B lymphopoiesis is blocked at the pro-B stage in the bone marrow of oc/oc mouse, leading to a low mature B-cell number. T-cell activation is also affected, with a reduction of IFNγ secretion by splenic CD4 T cells. These alterations are associated with a low IL-7 expression in bone marrow. All these data indicate that the lack of bone resorption in oc/oc mice has important consequences in both myelopoiesis and lymphopoiesis, leading to a form of immunodeficiency. The oc/oc mouse is therefore an appropriate model to understand the hematological defects described in IMO patients, and to derive new therapeutic strategies.</div></front></TEI><affiliations><list><country><li>Australie</li><li>France</li></country><region><li>Provence-Alpes-Côte d'Azur</li><li>Victoria (État)</li></region><settlement><li>Melbourne</li><li>Nice</li></settlement><orgName><li>Université de Melbourne</li></orgName></list><tree><country name="France"><region name="Provence-Alpes-Côte d'Azur"><name sortKey="Blin Wakkach, C" sort="Blin Wakkach, C" uniqKey="Blin Wakkach C" first="C." last="Blin-Wakkach">C. Blin-Wakkach</name></region><name sortKey="Carle, G F" sort="Carle, G F" uniqKey="Carle G" first="G. F." last="Carle">G. F. Carle</name><name sortKey="Rochet, N" sort="Rochet, N" uniqKey="Rochet N" first="N." last="Rochet">N. Rochet</name><name sortKey="Wakkach, A" sort="Wakkach, A" uniqKey="Wakkach A" first="A." last="Wakkach">A. Wakkach</name></country><country name="Australie"><region name="Victoria (État)"><name sortKey="Sexton, P M" sort="Sexton, P M" uniqKey="Sexton P" first="P. M." last="Sexton">P. M. Sexton</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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