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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
4
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pubmed:dateCreated |
2007-2-7
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pubmed:abstractText |
Neurofibromatosis type 1 (NF1) syndrome is caused by germline mutations in the NF1 tumor suppressor, which encodes neurofibromin, a GTPase activating protein for Ras. Children with NF1 are predisposed to juvenile myelomonocytic leukemia (JMML) and lethally irradiated mice given transplants with homozygous Nf1 mutant (Nf1-/-) hematopoietic stem cells develop a fatal myeloproliferative disorder (MPD) that models JMML. We investigated the requirement for signaling through the GM-CSF receptor to initiate and sustain this MPD by generating Nf1 mutant hematopoietic cells lacking the common beta chain (Beta c) of the GM-CSF receptor. Mice reconstituted with Nf1-/-, beta c-/- stem cells did not develop evidence of MPD despite the presence of increased number of immature hematopoietic progenitors in the bone marrow. Interestingly, when the Mx1-Cre transgene was used to inactivate a conditional Nf1 mutant allele in hematopoietic cells, concomitant loss of beta c-/- reduced the severity of the MPD, but did not abrogate it. Whereas inhibiting GM-CSF signaling may be of therapeutic benefit in JMML, our data also demonstrate aberrant proliferation of Nf1-/-myeloid progenitors that is independent of signaling through the GM-CSF receptor.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/17090653-10372132,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17090653-10678181,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17090653-10967421,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17090653-11297510,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17090653-11544276,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17090653-11988578,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17090653-14982883,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17090653-1568246,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17090653-15781578,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17090653-2116237,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17090653-6798842,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17090653-7697542,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17090653-7920653,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17090653-7926784,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17090653-8563750,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17090653-8563751,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17090653-8839857,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17090653-8947912,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17090653-9107407,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17090653-9323135,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17090653-9376581,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17090653-9389708,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17090653-9607929
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0006-4971
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pubmed:author |
pubmed-author:DiersMiechaleen DMD,
pubmed-author:GeurtsJennifer LJL,
pubmed-author:HaszDiane EDE,
pubmed-author:KimAndrewA,
pubmed-author:KoganScott CSC,
pubmed-author:LargaespadaDavid ADA,
pubmed-author:LauchleJennifer OJO,
pubmed-author:LeDoan TDT,
pubmed-author:MorganKellyK,
pubmed-author:ParadaLuis FLF,
pubmed-author:ShannonKevinK,
pubmed-author:WiesnerStephen MSM
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
109
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1687-91
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:17090653-Animals,
pubmed-meshheading:17090653-Disease Models, Animal,
pubmed-meshheading:17090653-Hematopoietic Stem Cell Transplantation,
pubmed-meshheading:17090653-Leukemia, Myelomonocytic, Chronic,
pubmed-meshheading:17090653-Mice,
pubmed-meshheading:17090653-Mice, Mutant Strains,
pubmed-meshheading:17090653-Myeloproliferative Disorders,
pubmed-meshheading:17090653-Neurofibromatosis 1,
pubmed-meshheading:17090653-Receptors, Granulocyte-Macrophage Colony-Stimulating Factor,
pubmed-meshheading:17090653-Signal Transduction
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pubmed:year |
2007
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pubmed:articleTitle |
Beta common receptor inactivation attenuates myeloproliferative disease in Nf1 mutant mice.
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pubmed:affiliation |
Department of Pediatrics, University of California San Francisco, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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