Genetic Basis of Hypo-Responsiveness of A/J Mice to Interleukin-3
Hematopoietic progenitor cells of the A/J strain of mice show a pronounced defect in the ability to form colonies or proliferate in response to interleukin-3 (IL-3). Comparison of immunoblots of A/J mast cells and of mast cells from the C57BL/6 strain that respond normally to IL-3 showed that, in bo...
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description | Hematopoietic progenitor cells of the A/J strain of mice show a pronounced defect in the ability to form colonies or proliferate in response to interleukin-3 (IL-3). Comparison of immunoblots of A/J mast cells and of mast cells from the C57BL/6 strain that respond normally to IL-3 showed that, in both strains, a 125-kD band of the expected size was recognized by an antibody against the β chain of the IL-3 receptor, the AIC2A molecule. However, in the C57BL/6 cells, there was an additional 110-kD species not seen in cells of the A/J strain. Analyses using bone marrow-derived mast cells from a panel of A/J x C57BL/6 and A/J x C57BL/6 recombinant inbred (Rl) mice showed that the hypo-responsiveness to IL-3 is governed by a single gene. However, the absence of this 110-kD species in the A/J strain did not co-map with IL-3 hypo-responsiveness but did indeed map to the AIC2A genetic locus. These data show that this trait in the A/J strain was due to a polymorphism of the AIC2A gene unrelated to IL-3 hypo-responsiveness. Typing of the Rl strains for the markers D14MH98, D14Mit14, and D14Mit133 mapped the locus determining hypo-responsiveness to IL-3 to the subtelomeric region of chromosome 14, the region that also bears the gene encoding the α chain of the IL-3 receptor (IL-3Rα). Immunofluorescence analyses indicated that IL-3Rα protein was undetectable on fresh bone marrow cells from A/J mice, although clearly detectable on cells from the responder C57BL/6 strain. However, IL-3Rα was readily detectable at normal levels on A/J mast cells generated by culture of A/J bone marrow cells in a combination of IL-3 and steel factor. Moreover, IL-3Rα on these A/J mast cells appears to be functional in that IL-3 stimulation of these cells results in tyrosine phosphorylation events characteristic of IL-3 signaling, including tyrosine phosphorylation of the β chain of the IL-3 receptor, Jak-2 kinase, and SHPTP2. Collectively, these data indicate that the hypo-responsiveness of A/J mice to IL-3 is due to a defect in the gene encoding IL-3Rα and that, although this defect gives rise to reduced expression of α chain on primary bone marrow cells, this defect is not absolute and that, under certain circumstances, A/J cells can express functional receptors. |
doi_str_mv | 10.1182/blood.V87.8.3186.bloodjournal8783186 |
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Comparison of immunoblots of A/J mast cells and of mast cells from the C57BL/6 strain that respond normally to IL-3 showed that, in both strains, a 125-kD band of the expected size was recognized by an antibody against the β chain of the IL-3 receptor, the AIC2A molecule. However, in the C57BL/6 cells, there was an additional 110-kD species not seen in cells of the A/J strain. Analyses using bone marrow-derived mast cells from a panel of A/J x C57BL/6 and A/J x C57BL/6 recombinant inbred (Rl) mice showed that the hypo-responsiveness to IL-3 is governed by a single gene. However, the absence of this 110-kD species in the A/J strain did not co-map with IL-3 hypo-responsiveness but did indeed map to the AIC2A genetic locus. These data show that this trait in the A/J strain was due to a polymorphism of the AIC2A gene unrelated to IL-3 hypo-responsiveness. Typing of the Rl strains for the markers D14MH98, D14Mit14, and D14Mit133 mapped the locus determining hypo-responsiveness to IL-3 to the subtelomeric region of chromosome 14, the region that also bears the gene encoding the α chain of the IL-3 receptor (IL-3Rα). Immunofluorescence analyses indicated that IL-3Rα protein was undetectable on fresh bone marrow cells from A/J mice, although clearly detectable on cells from the responder C57BL/6 strain. However, IL-3Rα was readily detectable at normal levels on A/J mast cells generated by culture of A/J bone marrow cells in a combination of IL-3 and steel factor. Moreover, IL-3Rα on these A/J mast cells appears to be functional in that IL-3 stimulation of these cells results in tyrosine phosphorylation events characteristic of IL-3 signaling, including tyrosine phosphorylation of the β chain of the IL-3 receptor, Jak-2 kinase, and SHPTP2. Collectively, these data indicate that the hypo-responsiveness of A/J mice to IL-3 is due to a defect in the gene encoding IL-3Rα and that, although this defect gives rise to reduced expression of α chain on primary bone marrow cells, this defect is not absolute and that, under certain circumstances, A/J cells can express functional receptors.</description><identifier>ISSN: 0006-4971</identifier><identifier>EISSN: 1528-0020</identifier><identifier>DOI: 10.1182/blood.V87.8.3186.bloodjournal8783186</identifier><identifier>PMID: 8605333</identifier><language>eng</language><publisher>Washington, DC: Elsevier Inc</publisher><subject>Animals ; Base Sequence ; Biological and medical sciences ; Cell differentiation, maturation, development, hematopoiesis ; Cell physiology ; Cells, Cultured ; Chromosome Mapping ; Fundamental and applied biological sciences. Psychology ; Gene Expression ; Hematopoiesis - drug effects ; Hematopoietic Stem Cells - drug effects ; Interleukin-3 - pharmacology ; Mice ; Mice, Inbred A - genetics ; Mice, Inbred C57BL ; Mice, Inbred DBA ; Molecular and cellular biology ; Molecular Sequence Data ; Polymorphism, Genetic ; Receptors, Interleukin-3 - chemistry ; Receptors, Interleukin-3 - deficiency ; Receptors, Interleukin-3 - drug effects ; Receptors, Interleukin-3 - genetics ; Recombinant Proteins - pharmacology ; Signal Transduction - drug effects ; Species Specificity ; Stem Cell Factor - pharmacology</subject><ispartof>Blood, 1996-04, Vol.87 (8), p.3186-3194</ispartof><rights>1996 American Society of Hematology</rights><rights>1996 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c562t-37bd8846ba653d8934ffadae21200fa92a6614152f89f29a7127036669baadf53</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=3042621$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8605333$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Leslie, Kevin B.</creatorcontrib><creatorcontrib>Jalbert, Sheila</creatorcontrib><creatorcontrib>Orban, Paul</creatorcontrib><creatorcontrib>Welham, Melanie</creatorcontrib><creatorcontrib>Duronio, Vincent</creatorcontrib><creatorcontrib>Schrader, John W.</creatorcontrib><title>Genetic Basis of Hypo-Responsiveness of A/J Mice to Interleukin-3</title><title>Blood</title><addtitle>Blood</addtitle><description>Hematopoietic progenitor cells of the A/J strain of mice show a pronounced defect in the ability to form colonies or proliferate in response to interleukin-3 (IL-3). Comparison of immunoblots of A/J mast cells and of mast cells from the C57BL/6 strain that respond normally to IL-3 showed that, in both strains, a 125-kD band of the expected size was recognized by an antibody against the β chain of the IL-3 receptor, the AIC2A molecule. However, in the C57BL/6 cells, there was an additional 110-kD species not seen in cells of the A/J strain. Analyses using bone marrow-derived mast cells from a panel of A/J x C57BL/6 and A/J x C57BL/6 recombinant inbred (Rl) mice showed that the hypo-responsiveness to IL-3 is governed by a single gene. However, the absence of this 110-kD species in the A/J strain did not co-map with IL-3 hypo-responsiveness but did indeed map to the AIC2A genetic locus. These data show that this trait in the A/J strain was due to a polymorphism of the AIC2A gene unrelated to IL-3 hypo-responsiveness. Typing of the Rl strains for the markers D14MH98, D14Mit14, and D14Mit133 mapped the locus determining hypo-responsiveness to IL-3 to the subtelomeric region of chromosome 14, the region that also bears the gene encoding the α chain of the IL-3 receptor (IL-3Rα). Immunofluorescence analyses indicated that IL-3Rα protein was undetectable on fresh bone marrow cells from A/J mice, although clearly detectable on cells from the responder C57BL/6 strain. However, IL-3Rα was readily detectable at normal levels on A/J mast cells generated by culture of A/J bone marrow cells in a combination of IL-3 and steel factor. Moreover, IL-3Rα on these A/J mast cells appears to be functional in that IL-3 stimulation of these cells results in tyrosine phosphorylation events characteristic of IL-3 signaling, including tyrosine phosphorylation of the β chain of the IL-3 receptor, Jak-2 kinase, and SHPTP2. Collectively, these data indicate that the hypo-responsiveness of A/J mice to IL-3 is due to a defect in the gene encoding IL-3Rα and that, although this defect gives rise to reduced expression of α chain on primary bone marrow cells, this defect is not absolute and that, under certain circumstances, A/J cells can express functional receptors.</description><subject>Animals</subject><subject>Base Sequence</subject><subject>Biological and medical sciences</subject><subject>Cell differentiation, maturation, development, hematopoiesis</subject><subject>Cell physiology</subject><subject>Cells, Cultured</subject><subject>Chromosome Mapping</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Expression</subject><subject>Hematopoiesis - drug effects</subject><subject>Hematopoietic Stem Cells - drug effects</subject><subject>Interleukin-3 - pharmacology</subject><subject>Mice</subject><subject>Mice, Inbred A - genetics</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Inbred DBA</subject><subject>Molecular and cellular biology</subject><subject>Molecular Sequence Data</subject><subject>Polymorphism, Genetic</subject><subject>Receptors, Interleukin-3 - chemistry</subject><subject>Receptors, Interleukin-3 - deficiency</subject><subject>Receptors, Interleukin-3 - drug effects</subject><subject>Receptors, Interleukin-3 - genetics</subject><subject>Recombinant Proteins - pharmacology</subject><subject>Signal Transduction - drug effects</subject><subject>Species Specificity</subject><subject>Stem Cell Factor - pharmacology</subject><issn>0006-4971</issn><issn>1528-0020</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1996</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqVkEtLxDAUhYMoOj5-gtCFuLI1jzZNluNrRvEBom5Dmt5Axk4zJq3gv7fzYFZuXAXO-Ti5fAhdEJwRIuhl1XhfZx-izETGiODZKpj5PrS6EaVYZjtoRAoqUowp3kUjjDFPc1mSA3QY4wxjkjNa7KN9wXHBGBuh8QRa6JxJrnR0MfE2mf4sfPoKceHb6L6HNq7i8eVD8uQMJJ1P7tsOQgP9p2tTdoz2rG4inGzeI_R-d_t2PU0fXyb31-PH1BScdikrq1qInFeaF6wWkuXW6loDJRRjqyXVnJN8ON4KaanUJaElZpxzWWld24IdofP17iL4rx5ip-YuGmga3YLvoypLKSmXfABv1qAJPsYAVi2Cm-vwowhWS5NqJU4NJpVQS2vqD5PDzOnmv76aQ70d2agb-rNNr6PRjQ26NS5uMYZzyikZsOc1BoObbwdBReOgNVC7AKZTtXf_u-sX262c4Q</recordid><startdate>19960415</startdate><enddate>19960415</enddate><creator>Leslie, Kevin B.</creator><creator>Jalbert, Sheila</creator><creator>Orban, Paul</creator><creator>Welham, Melanie</creator><creator>Duronio, Vincent</creator><creator>Schrader, John W.</creator><general>Elsevier Inc</general><general>The Americain Society of Hematology</general><scope>6I.</scope><scope>AAFTH</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>19960415</creationdate><title>Genetic Basis of Hypo-Responsiveness of A/J Mice to Interleukin-3</title><author>Leslie, Kevin B. ; Jalbert, Sheila ; Orban, Paul ; Welham, Melanie ; Duronio, Vincent ; Schrader, John W.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c562t-37bd8846ba653d8934ffadae21200fa92a6614152f89f29a7127036669baadf53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1996</creationdate><topic>Animals</topic><topic>Base Sequence</topic><topic>Biological and medical sciences</topic><topic>Cell differentiation, maturation, development, hematopoiesis</topic><topic>Cell physiology</topic><topic>Cells, Cultured</topic><topic>Chromosome Mapping</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene Expression</topic><topic>Hematopoiesis - drug effects</topic><topic>Hematopoietic Stem Cells - drug effects</topic><topic>Interleukin-3 - pharmacology</topic><topic>Mice</topic><topic>Mice, Inbred A - genetics</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Inbred DBA</topic><topic>Molecular and cellular biology</topic><topic>Molecular Sequence Data</topic><topic>Polymorphism, Genetic</topic><topic>Receptors, Interleukin-3 - chemistry</topic><topic>Receptors, Interleukin-3 - deficiency</topic><topic>Receptors, Interleukin-3 - drug effects</topic><topic>Receptors, Interleukin-3 - genetics</topic><topic>Recombinant Proteins - pharmacology</topic><topic>Signal Transduction - drug effects</topic><topic>Species Specificity</topic><topic>Stem Cell Factor - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Leslie, Kevin B.</creatorcontrib><creatorcontrib>Jalbert, Sheila</creatorcontrib><creatorcontrib>Orban, Paul</creatorcontrib><creatorcontrib>Welham, Melanie</creatorcontrib><creatorcontrib>Duronio, Vincent</creatorcontrib><creatorcontrib>Schrader, John W.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Blood</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Leslie, Kevin B.</au><au>Jalbert, Sheila</au><au>Orban, Paul</au><au>Welham, Melanie</au><au>Duronio, Vincent</au><au>Schrader, John W.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genetic Basis of Hypo-Responsiveness of A/J Mice to Interleukin-3</atitle><jtitle>Blood</jtitle><addtitle>Blood</addtitle><date>1996-04-15</date><risdate>1996</risdate><volume>87</volume><issue>8</issue><spage>3186</spage><epage>3194</epage><pages>3186-3194</pages><issn>0006-4971</issn><eissn>1528-0020</eissn><abstract>Hematopoietic progenitor cells of the A/J strain of mice show a pronounced defect in the ability to form colonies or proliferate in response to interleukin-3 (IL-3). Comparison of immunoblots of A/J mast cells and of mast cells from the C57BL/6 strain that respond normally to IL-3 showed that, in both strains, a 125-kD band of the expected size was recognized by an antibody against the β chain of the IL-3 receptor, the AIC2A molecule. However, in the C57BL/6 cells, there was an additional 110-kD species not seen in cells of the A/J strain. Analyses using bone marrow-derived mast cells from a panel of A/J x C57BL/6 and A/J x C57BL/6 recombinant inbred (Rl) mice showed that the hypo-responsiveness to IL-3 is governed by a single gene. However, the absence of this 110-kD species in the A/J strain did not co-map with IL-3 hypo-responsiveness but did indeed map to the AIC2A genetic locus. These data show that this trait in the A/J strain was due to a polymorphism of the AIC2A gene unrelated to IL-3 hypo-responsiveness. Typing of the Rl strains for the markers D14MH98, D14Mit14, and D14Mit133 mapped the locus determining hypo-responsiveness to IL-3 to the subtelomeric region of chromosome 14, the region that also bears the gene encoding the α chain of the IL-3 receptor (IL-3Rα). Immunofluorescence analyses indicated that IL-3Rα protein was undetectable on fresh bone marrow cells from A/J mice, although clearly detectable on cells from the responder C57BL/6 strain. However, IL-3Rα was readily detectable at normal levels on A/J mast cells generated by culture of A/J bone marrow cells in a combination of IL-3 and steel factor. Moreover, IL-3Rα on these A/J mast cells appears to be functional in that IL-3 stimulation of these cells results in tyrosine phosphorylation events characteristic of IL-3 signaling, including tyrosine phosphorylation of the β chain of the IL-3 receptor, Jak-2 kinase, and SHPTP2. Collectively, these data indicate that the hypo-responsiveness of A/J mice to IL-3 is due to a defect in the gene encoding IL-3Rα and that, although this defect gives rise to reduced expression of α chain on primary bone marrow cells, this defect is not absolute and that, under certain circumstances, A/J cells can express functional receptors.</abstract><cop>Washington, DC</cop><pub>Elsevier Inc</pub><pmid>8605333</pmid><doi>10.1182/blood.V87.8.3186.bloodjournal8783186</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Animals Base Sequence Biological and medical sciences Cell differentiation, maturation, development, hematopoiesis Cell physiology Cells, Cultured Chromosome Mapping Fundamental and applied biological sciences. Psychology Gene Expression Hematopoiesis - drug effects Hematopoietic Stem Cells - drug effects Interleukin-3 - pharmacology Mice Mice, Inbred A - genetics Mice, Inbred C57BL Mice, Inbred DBA Molecular and cellular biology Molecular Sequence Data Polymorphism, Genetic Receptors, Interleukin-3 - chemistry Receptors, Interleukin-3 - deficiency Receptors, Interleukin-3 - drug effects Receptors, Interleukin-3 - genetics Recombinant Proteins - pharmacology Signal Transduction - drug effects Species Specificity Stem Cell Factor - pharmacology |
title | Genetic Basis of Hypo-Responsiveness of A/J Mice to Interleukin-3 |
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