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The protein tyrosine kinase p60c-Src is not implicated in the pathogenesis of the human autosomal recessive form of osteopetrosis: A study of 13 children

Identifieur interne : 009861 ( Main/Exploration ); précédent : 009860; suivant : 009862

The protein tyrosine kinase p60c-Src is not implicated in the pathogenesis of the human autosomal recessive form of osteopetrosis: A study of 13 children

Auteurs : Frédéric Bernard ; Jean-Laurent Casanova ; Giulia Cournot ; Nada Jabado ; Jane Peake ; Sébastien Jauliac ; Alain Fischer ; Claire Hivroz

Source :

RBID : ISTEX:02E96B0B7BA0CBC53419B183E7820C984910DDA2

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English descriptors

Abstract

Abstract: Osteopetrosis has been described in mice generated by homozygous gene disruption of c-src gene encoding for the p60c-Src protein tyrosine kinase (Src –/– mice). The similarities of bone histologic findings in this murine model to those observed in some patients first seen with autosomal recessive osteopetrosis, “malignant” osteopetrosis, led us to investigate the potential role of p60c-Src in the pathogenesis of malignant osteopetrosis in 13 children. In 4 patients a c-src mutation was ruled out by an intragenic microsatellite segregation study. In the other 9 we analyzed p60c-Src expression and function, as well as c-src sequence. The expression was normal in all of the patients tested. In addition, the tyrosine phosphorylation and kinase activity of p60c-Src were also normal in all of the patients. Moreover, in these patients, sequences of the coding region of c-src were identical to the published sequence of the human c-src complementary DNA. These results exclude a role for c-src in the pathogenesis of human malignant osteopetrosis in the 13 patients analyzed. (J Pediatr 1998;133:537-43)

Url:
DOI: 10.1016/S0022-3476(98)70064-2


Affiliations:


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Le document en format XML

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<term>Adenosine triphosphate</term>
<term>Autosomal</term>
<term>Autosomal recessive osteopetrosis</term>
<term>Bone marrow cells</term>
<term>Bone marrow transplantation</term>
<term>Bone matrix proteins</term>
<term>Bone resorption</term>
<term>Bone surface</term>
<term>Border formation</term>
<term>Calcif tissue</term>
<term>Carbonic anhydrase</term>
<term>Cell lines</term>
<term>Coding region</term>
<term>Donor bone marrow transplantation</term>
<term>EBV</term>
<term>Fibroblast</term>
<term>Generic term</term>
<term>Human gene</term>
<term>Immune complexes</term>
<term>Immuno electron microscopy</term>
<term>Intronic region</term>
<term>Keith bonham</term>
<term>Kinase</term>
<term>Kinase activity</term>
<term>Kinase buffer</term>
<term>Lysates</term>
<term>Malignant</term>
<term>Malignant osteopetrosis</term>
<term>Microsatellite</term>
<term>Microsatellite study</term>
<term>Molecular dynamics</term>
<term>Normal donors</term>
<term>Normal littermates</term>
<term>Osteoblast defect</term>
<term>Osteoclast</term>
<term>Osteoclast function</term>
<term>Osteopetrosis</term>
<term>Osteopetrotic mouse</term>
<term>Other patients</term>
<term>PCR</term>
<term>Pathogenesis</term>
<term>Pcrii vector</term>
<term>Pediatrics</term>
<term>Pediatrics october</term>
<term>Pediatrics volume</term>
<term>Pertussis</term>
<term>Pertussis incidence</term>
<term>Phosphor imager</term>
<term>Postnuclear lysates</term>
<term>Potential role</term>
<term>Proc natl acad</term>
<term>Protein tyrosine kinase</term>
<term>Recessive</term>
<term>Resorption</term>
<term>Saskatoon cancer centre</term>
<term>Similar results</term>
<term>Sodium dodecylsulfate polyacrylamide</term>
<term>Sodium ortho vanadate</term>
<term>Supportive care</term>
<term>Supportive measures</term>
<term>Transplantation</term>
<term>Tyrosine phosphorylation</term>
<term>Vaccine</term>
<term>Western blot analysis</term>
<term>mAb</term>
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<term>Acellular pertussis vaccines</term>
<term>Adenosine triphosphate</term>
<term>Autosomal</term>
<term>Autosomal recessive osteopetrosis</term>
<term>Bone marrow cells</term>
<term>Bone marrow transplantation</term>
<term>Bone matrix proteins</term>
<term>Bone resorption</term>
<term>Bone surface</term>
<term>Border formation</term>
<term>Calcif tissue</term>
<term>Carbonic anhydrase</term>
<term>Cell lines</term>
<term>Coding region</term>
<term>Donor bone marrow transplantation</term>
<term>Fibroblast</term>
<term>Generic term</term>
<term>Human gene</term>
<term>Immune complexes</term>
<term>Immuno electron microscopy</term>
<term>Intronic region</term>
<term>Keith bonham</term>
<term>Kinase</term>
<term>Kinase activity</term>
<term>Kinase buffer</term>
<term>Lysates</term>
<term>Malignant</term>
<term>Malignant osteopetrosis</term>
<term>Microsatellite</term>
<term>Microsatellite study</term>
<term>Molecular dynamics</term>
<term>Normal donors</term>
<term>Normal littermates</term>
<term>Osteoblast defect</term>
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<term>Osteopetrosis</term>
<term>Osteopetrotic mouse</term>
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<term>Pathogenesis</term>
<term>Pcrii vector</term>
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<term>Pediatrics volume</term>
<term>Pertussis</term>
<term>Pertussis incidence</term>
<term>Phosphor imager</term>
<term>Postnuclear lysates</term>
<term>Potential role</term>
<term>Proc natl acad</term>
<term>Protein tyrosine kinase</term>
<term>Recessive</term>
<term>Resorption</term>
<term>Saskatoon cancer centre</term>
<term>Similar results</term>
<term>Sodium dodecylsulfate polyacrylamide</term>
<term>Sodium ortho vanadate</term>
<term>Supportive care</term>
<term>Supportive measures</term>
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<term>Tyrosine phosphorylation</term>
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<div type="abstract" xml:lang="en">Abstract: Osteopetrosis has been described in mice generated by homozygous gene disruption of c-src gene encoding for the p60c-Src protein tyrosine kinase (Src –/– mice). The similarities of bone histologic findings in this murine model to those observed in some patients first seen with autosomal recessive osteopetrosis, “malignant” osteopetrosis, led us to investigate the potential role of p60c-Src in the pathogenesis of malignant osteopetrosis in 13 children. In 4 patients a c-src mutation was ruled out by an intragenic microsatellite segregation study. In the other 9 we analyzed p60c-Src expression and function, as well as c-src sequence. The expression was normal in all of the patients tested. In addition, the tyrosine phosphorylation and kinase activity of p60c-Src were also normal in all of the patients. Moreover, in these patients, sequences of the coding region of c-src were identical to the published sequence of the human c-src complementary DNA. These results exclude a role for c-src in the pathogenesis of human malignant osteopetrosis in the 13 patients analyzed. (J Pediatr 1998;133:537-43)</div>
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