公开(公告)号：WO2008057233A9

公开(公告)日：2008-07-24

申请号：PCT/US2007022600

申请日：2007-10-24

Applicant: UNIV CALIFORNIA ,  JAMIESON CATRIONA HELEN M ,  KAUSHANSKY KEN ,  BARROGA CHARLENE ,  GERON IFAT ,  ABRAHAMSON ANNELIE ,  KAVALERCHIK EDWARD

Inventor： JAMIESON CATRIONA HELEN M ,  KAUSHANSKY KEN ,  BARROGA CHARLENE ,  GERON IFAT ,  ABRAHAMSON ANNELIE ,  KAVALERCHIK EDWARD

IPC: A01K67/027

CPC classification number: A01K67/0271 ,  A01K2207/15 ,  A01K2217/00 ,  A01K2227/105 ,  A01K2267/0381 ,  C12N9/1205 ,  G01N33/5088

Abstract: Non human animal models are provided for diseases involving erythroid function, particularly myeloproliferative disease. The models are useful for testing and screening of biologically active agents that affect erythropoiesis, and erythroid function. In the animal models of the invention, a hematopoietic stem or progenitor cell (HSC) population that has been genetically altered by the introduction of a mutant JAK2 coding sequence is transplanted into an immunocompromised, xenogeneic, non-human recipient. The recipient animal is engrafted with the cell population at a high frequency, and develops a myeloproliferative disorder characterized by polycythemia.

Abstract translation: 非人类动物模型适用于涉及红系功能的疾病，特别是骨髓增生性疾病。 该模型对于影响红细胞生成和红细胞功能的生物活性剂的测试和筛选是有用的。 在本发明的动物模型中，通过引入突变体JAK2编码序列遗传改变的造血干细胞或祖细胞（HSC）群体被移植到免疫受损的异种非人受体中。 受体动物以高频率移植细胞群，并发展出以红细胞增多症为特征的骨髓增生性疾病。

公开(公告)号：WO2008057233A2

公开(公告)日：2008-05-15

申请号：PCT/US2007/022600

申请日：2007-10-24

Applicant: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA ,  JAMIESON, Catriona Helen, M. ,  KAUSHANSKY, Ken ,  BARROGA, Charlene ,  GERON, Ifat ,  ABRAHAMSON, Annelie ,  KAVALERCHIK, Edward

Inventor： JAMIESON, Catriona Helen, M. ,  KAUSHANSKY, Ken ,  BARROGA, Charlene ,  GERON, Ifat ,  ABRAHAMSON, Annelie ,  KAVALERCHIK, Edward

IPC: A01K67/027

CPC classification number: A01K67/0271 ,  A01K2207/15 ,  A01K2217/00 ,  A01K2227/105 ,  A01K2267/0381 ,  C12N9/1205 ,  G01N33/5088

Abstract: Non human animal models are provided for diseases involving erythroid function, particularly myeloproliferative disease. The models are useful for testing and screening of biologically active agents that affect erythropoiesis, and erythroid function. In the animal models of the invention, a hematopoietic stem or progenitor cell (HSC) population that has been genetically altered by the introduction of a mutant JAK2 coding sequence is transplanted into an immunocompromised, xenogeneic, non-human recipient. The recipient animal is engrafted with the cell population at a high frequency, and develops a myeloproliferative disorder characterized by polycythemia.

Abstract translation: 提供非人类动物模型用于涉及类红细胞功能，特别是骨髓增殖性疾病的疾病。 这些模型可用于测试和筛选影响红细胞生成和红细胞功能的生物活性剂。 在本发明的动物模型中，已经通过引入突变JAK2编码序列而遗传改变的造血干细胞或祖细胞（HSC）群体被移植到免疫受损的异种非人受体中。 受体动物以高频率植入细胞群，并且发展出以红血球增多症为特征的骨髓增生性疾病。

公开(公告)号：WO2008073619A2

公开(公告)日：2008-06-19

申请号：PCT/US2007083532

申请日：2007-11-02

Applicant: UNIV CALIFORNIA ,  JAMIESON CATRIONA HELEN M ,  GERON IFAT ,  ABRAHAMSON ANNELIE ,  KAVALERCHIK EDWARD ,  WEISSMAN IRVING L ,  GOTTLIB JASON

Inventor： JAMIESON CATRIONA HELEN M ,  GERON IFAT ,  ABRAHAMSON ANNELIE ,  KAVALERCHIK EDWARD ,  WEISSMAN IRVING L ,  GOTTLIB JASON

IPC: C12Q1/68

CPC classification number: C12N9/1294 ,  A01K67/0271 ,  A01K2227/105 ,  A01K2267/0331 ,  C12Q1/6886 ,  C12Q2600/112 ,  C12Q2600/118 ,  C12Q2600/136

Abstract: Cancer specific splicing events in the Wnt/ß -catenin signaling pathway are associated with progression of myelogenous leukemia. Misspliced genes of interest include GSK3ß. In some embodiments of the invention, polynucleotides are provided that correspond to misspliced GSK3ß transcripts associated with cancer. Such transcripts are characterized by a deletion of exon (8), and particularly in exon (8) and (9). Detection of such transcripts in cells is indicative of the presence of leukemia, and particularly of the presence of leukemia stem cells. In other embodiments, polypeptides are provided that are encoded by misspliced GSK3ß transcripts associated with cancer. Such polypeptides are useful as diagnostic markers for cancer, and as a target for screening of therapeutic agents. Animal models comprising a human LSC having a misspliced GSK3b transcript provide a useful model for leukemia, for drug/gene screening in the prevention and treatment of leukemia in humans, etc.

Abstract translation: Wnt /β-catenin信号通路中的癌细胞特异性剪接事件与骨髓性白血病的进展有关。 感兴趣的未知基因包括GSK3β。 在本发明的一些实施方案中，提供了与癌症相关的错过的GSK3β转录物相应的多核苷酸。 这些转录物的特征在于外显子（8）的缺失，特别是在外显子（8）和（9）中。 细胞中这些转录物的检测表明存在白血病，特别是存在白血病干细胞。 在其它实施方案中，提供由与癌症相关的错过的GSK3β转录物编码的多肽。 这样的多肽可用作癌症的诊断标记物，以及用作筛选治疗剂的靶标。 包含具有错误的GSK3b转录物的人LSC的动物模型为白血病提供了有用的模型，用于预防和治疗人类白血病等的药物/基因筛选。

公开(公告)号：WO2008057233A3

公开(公告)日：2008-10-30

申请号：PCT/US2007022600

申请日：2007-10-24

Applicant: UNIV CALIFORNIA ,  JAMIESON CATRIONA HELEN M ,  KAUSHANSKY KEN ,  BARROGA CHARLENE ,  GERON IFAT ,  ABRAHAMSON ANNELIE ,  KAVALERCHIK EDWARD

Inventor： JAMIESON CATRIONA HELEN M ,  KAUSHANSKY KEN ,  BARROGA CHARLENE ,  GERON IFAT ,  ABRAHAMSON ANNELIE ,  KAVALERCHIK EDWARD

IPC: G01N33/00 ,  A01K67/00 ,  A01K67/033 ,  C12N15/00

CPC classification number: A01K67/0271 ,  A01K2207/15 ,  A01K2217/00 ,  A01K2227/105 ,  A01K2267/0381 ,  C12N9/1205 ,  G01N33/5088

Abstract: Non human animal models are provided for diseases involving erythroid function, particularly myeloproliferative disease. The models are useful for testing and screening of biologically active agents that affect erythropoiesis, and erythroid function. In the animal models of the invention, a hematopoietic stem or progenitor cell (HSC) population that has been genetically altered by the introduction of a mutant JAK2 coding sequence is transplanted into an immunocompromised, xenogeneic, non-human recipient. The recipient animal is engrafted with the cell population at a high frequency, and develops a myeloproliferative disorder characterized by polycythemia.

Abstract translation: 提供非人类动物模型用于涉及类红细胞功能，特别是骨髓增殖性疾病的疾病。 这些模型可用于测试和筛选影响红细胞生成和红细胞功能的生物活性剂。 在本发明的动物模型中，已经通过引入突变JAK2编码序列而遗传改变的造血干细胞或祖细胞（HSC）群体被移植到免疫受损的异种非人受体中。 受体动物以高频率植入细胞群体，并发展出以红血球增多症为特征的骨髓增生性疾病。

公开(公告)号：WO2008073619A3

公开(公告)日：2008-06-19

申请号：PCT/US2007/083532

申请日：2007-11-02

Applicant: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA ,  JAMIESON, Catriona, Helen, M. ,  GERON, Ifat ,  ABRAHAMSON, Annelie ,  KAVALERCHIK, Edward ,  WEISSMAN, Irving, L. ,  GOTTLIB, Jason

Inventor： JAMIESON, Catriona, Helen, M. ,  GERON, Ifat ,  ABRAHAMSON, Annelie ,  KAVALERCHIK, Edward ,  WEISSMAN, Irving, L. ,  GOTTLIB, Jason

IPC: C12Q1/00 ,  C12Q1/68 ,  G01N33/53 ,  G01N33/574

Abstract: Cancer specific splicing events in the Wnt/β -catenin signaling pathway are associated with progression of myelogenous leukemia. Misspliced genes of interest include GSK3β. In some embodiments of the invention, polynucleotides are provided that correspond to misspliced GSK3β transcripts associated with cancer. Such transcripts are characterized by a deletion of exon (8), and particularly in exon (8) and (9). Detection of such transcripts in cells is indicative of the presence of leukemia, and particularly of the presence of leukemia stem cells. In other embodiments, polypeptides are provided that are encoded by misspliced GSK3β transcripts associated with cancer. Such polypeptides are useful as diagnostic markers for cancer, and as a target for screening of therapeutic agents. Animal models comprising a human LSC having a misspliced GSK3b transcript provide a useful model for leukemia, for drug/gene screening in the prevention and treatment of leukemia in humans, etc.