ライフサイエンスコーパス: XSCID

1 XSCID dogs < 3 wk of age had an elevated number of B cel

2 XSCID was found to result from mutations in the interleu

3 ddress these questions, we have developed an XSCID mouse model in which both the Arf tumor-suppressor

4 orrective gene transfer was applicable to an XSCID murine model with preserved expression of a trunca

5 ) cells using MFGS-gc retrovirus may benefit XSCID patients with persistent T- and B-cell deficits de

6 Bone marrow-transplanted (BMT) XSCID dogs not only engraft donor T cells and reconstitu

7 nitors by the expression of normal gamma(c), XSCID is a good candidate disease for therapeutic retrov

8 Gene correction of Deltagamma(c+)-XSCID mice resulted in the reconstitution of lymphoid de

9 atically reduced in untreated Deltagamma(c+)-XSCID mice.

10 a truncated gammac molecule (Deltagamma(c+)-XSCID).

11 Canine XSCID therefore provides an ideal animal model with whic

12 Canine XSCID, like human XSCID, is due to mutations in the comm

13 Although human and canine XSCID share similar features, such as a failure to thriv

14 Thus, canine XSCID provides a model to determine the optimal conditio

15 ed severe combined immunodeficiency disease (XSCID) in both humans and dogs results from mutations in

16 ed severe combined immunodeficiency disease (XSCID).

17 e feasibility of a gene therapy approach for XSCID, a retroviral vector expressing gamma-c was used t

18 ecause bone marrow transplantation (BMT) for XSCID does not provide complete immune reconstitution fo

19 erapy is a feasible therapeutic strategy for XSCID.

20 ever, only transduced gamma progenitors from XSCID patients developed into T and B cells.

21 Both canine and human XSCID are caused by defects in the common gamma chain, g

22 virus infection recently described for human XSCID patients following BMT.

23 Unlike the experience in human XSCID patients, all three dogs engrafted both donor B an

24 Canine XSCID, like human XSCID, is due to mutations in the common gamma chain (ga

25 cells, phenotypically resembling most human XSCID patients.

26 nologic features identical to those of human XSCID, making it a true homolog of the human disease.

27 ical clinically and immunologically to human XSCID, making it a true homologue of the human disease.

28 ether SCC will develop in transplanted human XSCID patients later in life.

29 ntrast to the majority of transplanted human XSCID patients, also engraft donor B cells and reconstit

30 turn advance similar efforts to treat human XSCID.

31 e X-linked severe combined immunodeficiency (XSCID) and in turn advance similar efforts to treat huma

32 h X-linked severe combined immunodeficiency (XSCID) caused by mutations in the IL2RG gene encoding th

33 r X-linked severe combined immunodeficiency (XSCID) has shown that retroviral-mediated gene correctio

34 X-linked severe combined immunodeficiency (XSCID) is a lethal disease caused by a defect in the gen

35 X-linked severe combined immunodeficiency (XSCID) is a life-threatening syndrome in which both cell

36 X-linked severe combined immunodeficiency (XSCID) is an inherited disease characterized by profound

37 X-linked severe combined immunodeficiency (XSCID) is caused by mutations of the common gamma chain

38 e X-linked severe combined immunodeficiency (XSCID) is due to mutations in the common gamma chain (ga

39 t X-linked severe combined immunodeficiency (XSCID) lymphoblastoid cell line JT, and JT cells reconst

40 n X-linked severe combined immunodeficiency (XSCID) without pretransplant conditioning results in eng

41 In XSCID and SCID resulting from mutations in JAK3, which e

42 in neonates to < 40% by 3 to 5 yr of age, in XSCID dogs a rapid decline in the percentage of CD45RA+

43 pearance of nonmaternally derived T cells in XSCID dogs that undergo a rapid switch from CD45RA+ to C

44 t the T-cell, but not the NK-cell, defect in XSCID results from inactivation of IL-7Ralpha signalling

45 the phenotype and clinical manifestations in XSCID are more severe than the abnormalities found in hu

46 iated transduction of wild-type gamma c into XSCID JT cells restored function to the IL-21R, as shown

47 fter our initial report of successful BMT of XSCID dogs, it soon became evident that transplanted XSC

48 p model was exploited to test development of XSCID CD34(+) cells into mature myeloid and lymphoid lin

49 gamma(c)-deficient mice as a murine model of XSCID.

50 ot be strictly necessary for gene therapy of XSCID.

51 tion remains the most effective treatment of XSCID patients, better strategies are necessary to achie

52 gene therapy as salvage treatment for older XSCID children with inadequate immune reconstitution des

53 there unique risk factors for X-linked SCID (XSCID) gene therapy that increase the risk of insertiona

54 The most common form of SCID, X-linked SCID (XSCID), results from mutations in IL2RG, which encodes t

55 successful immune reconstitution in several XSCID mouse models, all carrying null mutations of the c

56 We studied XSCID patients who have persistent defects in B-cell and

57 l engraftment was not detected in any of the XSCID dogs by using a sensitive PCR assay.

58 ls appeared in approximately one-half of the XSCID dogs, although the absolute number of T cells was

59 linical benefit in humans affected with this XSCID.

60 rformed bone marrow transplantation in three XSCID dogs without pretransplant conditioning, using unt

61 After transduction, XSCID cells newly expressed gamma-c on the cell surface

62 Of 24 transplanted XSCID dogs followed for at least 1 year post-BMT, 71% de

63 gs, it soon became evident that transplanted XSCID dogs developed late-onset severe chronic cutaneous

64 Transduced and untransduced XSCID CD34(+) cells injected into developing sheep fetus

65 are observed in some affected dogs, whereas XSCID boys have few, if any, circulating T cells.

66 onsible for the B cell defect in humans with XSCID.

67 rmed B-cell lines derived from patients with XSCID.