Hematological defects in the oc/oc mouse, a model of infantile malignant osteopetrosis
Identifieur interne : 004B23 ( PascalFrancis/Checkpoint ); précédent : 004B22; suivant : 004B24Hematological 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.
Affiliations:
- Australie, France
- Provence-Alpes-Côte d'Azur, Victoria (État)
- Melbourne, Nice
- Université de Melbourne
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Pascal:04-0483813Le document en format XML
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<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>
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<fC01 i1="01" l="ENG"><s0>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.</s0>
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<s5>40</s5>
</fC07>
<fC07 i1="09" i2="X" l="FRE"><s0>Système ostéoarticulaire</s0>
<s5>41</s5>
</fC07>
<fC07 i1="09" i2="X" l="ENG"><s0>Osteoarticular system</s0>
<s5>41</s5>
</fC07>
<fC07 i1="09" i2="X" l="SPA"><s0>Sistema osteoarticular</s0>
<s5>41</s5>
</fC07>
<fN21><s1>271</s1>
</fN21>
<fN44 i1="01"><s1>OTO</s1>
</fN44>
<fN82><s1>OTO</s1>
</fN82>
</pA>
</standard>
</inist>
<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>
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