Focal segmental glomerular sclerosis, a type of intractable chronic glomerulonephritis, is a stem cell disorder.

Nishimura, Masanori; Toki, Junko; Sugiura, Kikuya; Hashimoto, Futoshi; Tomita, Takeshi; Fujishima, Hiroshi; Hiramatsu, Yasushi; Nishioka, N; Nagata, Norikazu; Y, Takahashi

doi:10.1084/jem.179.3.1053

Cited by 71 publications

(40 citation statements)

References 14 publications

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“…Given the fact that all three founder lines used in this study show transgene expression in kidney, the combined results from our studies favor the hypothesis that the primary lesion leading to nephropathy in Em-pp-Frat1 transgenic mice is kidney-borne instead of blood-borne. In this respect our ®ndings are in contrast with the observations of Nishimura et al (1994), who reported that transplantation of bone marrow cells or puri®ed hematopoietic stem cells from FGS mice in which FGS appears to be controlled by two pairs of autosomal recessive genes, can induce FGS in normal mice. The recent ®nding that Frat can activate the Wnt signal transduction pathway through inhibition of GSK3 kinase activity, raises the possibility that the nephropathy in Em-pp-Frat1 transgenic mice is caused by ectopic Wnt signaling activity in the (developing) kidney (Yost et al, 1998).…”

Section: Nephrotic Syndrome In Frat1 Transgenic Micecontrasting

confidence: 99%

Overexpression of Frat1 in transgenic mice leads to glomerulosclerosis and nephrotic syndrome, and provides direct evidence for the involvement of Frat1 in lymphoma progression

et al. 1999

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The proto-oncogene Frat1 was originally identi®ed as a common site of proviral insertion in transplanted tumors of Moloney murine leukemia virus (M-MuLV)-infected Em-Pim1 transgenic mice. Contrary to most common insertion sites implicated in mouse T cell lymphomagenesis, retroviral insertional mutagenesis of Frat1 constitutes a relatively late event in M-MuLV-induced tumor development, suggesting that proviral activation of Frat1 contributes to progression of T cell lymphomas rather than their genesis. To substantiate this notion we have generated transgenic mice that overexpress Frat1 in various organs, including lymphoid tissues. Frat1 transgenic mice develop focal glomerulosclerosis and a nephrotic syndrome, but they do not exhibit an increased incidence of spontaneous lymphomas. Conversely, these mice are highly susceptible to M-MuLV-induced lymphomagenesis, and Frat1/Pim1 bitransgenic animals develop lymphomas with increased frequency compared to Pim1 transgenic littermates. These data support a role for Frat1 in tumor progression.

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Section: Nephrotic Syndrome In Frat1 Transgenic Micecontrasting

confidence: 99%

Overexpression of Frat1 in transgenic mice leads to glomerulosclerosis and nephrotic syndrome, and provides direct evidence for the involvement of Frat1 in lymphoma progression

et al. 1999

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“…In contrast, there are some reports showing that FTBI is less effective in the treatment of malignant tumors, particularly leukemias, than single high-dose irradiation. 2,3 We have previously demonstrated that allogeneic BMT can be used to treat both systemic and organ-specific autoimmune diseases, [4][5][6][7][8] and that autoimmune diseases are stem cell disorders. 5 The MRL/lpr mouse, an animal model for systemic lupus erythematosus (SLE), is known to be radiosensitive (particularly after the onset of the disease); almost all the mice die as a result of intestinal damage when irradiated with more than 8.5 Gy, and lower doses do not remove abnormal hemopoietic stem cells of MRL/lpr mice.…”

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confidence: 99%

Optimal protocol for total body irradiation for allogeneic bone marrow transplantation in mice

Hisha

et al. 2002

Bone Marrow Transplant

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Summary:We have previously demonstrated, using chimeric resistant MRL/lpr mice, that a fractionated total body irradiation (FTBI) (5 Gy ؋ 2 with a 4 h interval on the day before allogeneic bone marrow transplantation (BMT) ) is the best conditioning regimen for the treatment of autoimmune diseases in radiosensitive MRL/lpr mice. In the present study, using various standard strains of mice (not radiosensitive mice), we explore the best protocol for irradiation (doses and intervals) as the conditioning regimen for allogeneic BMT. Recipient mice were exposed to various irradiation regimens: a single total body irradiation (TBI) of 9.5 or 12 Gy and FTBI of (5+5) Gy to (7+7) Gy with a 1 to 24 h interval. The method generally utilized for humans ((2+2) Gy with a 4 h interval for 3 days (total 12 Gy)) was also used. One day after the last irradiation, donor BMCs from BALB/c, C3H, or C57BL/6 (B6) mice were transplanted into C3H or B6 mice. The irradiation protocol of (2+2) Gy for 3 days was found to be insufficient to enable the complete removal of recipient immunocompetent cells, since donor-reactive T cells were observed in the recipient spleens and many recipient-type NK and CD4 + cells were also detected in the recipient hematolymphoid tissues. In all the combinations, the highest survival rate was achieved in the recipients irradiated with (6+6) or (6.5+6.5) Gy with a 4 h interval. In the surviving mice, the hematolymphoid tissues had been fully reconstituted with donor cells. Bone Marrow Transplantation (2002) 30, 843-849. doi:10.1038/sj.bmt.1703766 Keywords: bone marrow transplantation; fractionated irradiation; reconstitution Irradiation has been used as an effective conditioning regimen for bone marrow transplantation (BMT), since it kills rapidly proliferating immunocompetent cells, particularly T

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“…This mouse strain was established from offspring at the F5 generation of an outcross between CBA/N and RFM/ Nga strains, and FGS/Nga mice have been reported as three types: mice with high proteinuria and wasting syndrome, mice with high proteinuria only, and normal mice [11]. In previous studies, general features such as genetic profile, immunohistochemical and electron microscopical findings for the renal lesion were investigated, and bone marrow stem cell disorder has been suggested as a causative factor for the glomerulosclerosis development of FGS/Nga mice [13,23]. Recently, it has also been reported that recombinant interleukin-10 gene injection to the kidneys of this mouse reduced the development of glomerulocsclerosis [3].…”

Section: Introductionmentioning

confidence: 99%

Changes of Renal Lesion-Related Parameters in FGS/Nga and the Parental Mouse Strains, CBA/N and RFM/Nga.

Kim

Choi²,

Lee

et al. 2004

Exp. Anim.

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Abstract:The FGS/Nga mouse strain, established from an outcross between CBA/N and RFM/Nga mice strains, has previously been reported as a spontaneous mouse model for focal glomerular sclerosis (FGS) and is considered to have two pairs of autosomal recessive genes associated with FGS. In this study, we examined the changes of seven renal lesion-related parameters, blood urea nitrogen (BUN), creatinine, albumin and total protein in plasma, urinary protein, systolic blood pressure, and a glomerulosclerosis index on histological observation, in 20-week-old FGS/Nga mice and their age-matched two parental strains, CBA/N and RFM/Nga. The levels of plasma BUN and creatinine, urinary protein and systolic blood pressure were significantly increased in FGS/Nga, compared with those of the parental strains. RFM/Nga mice showed slightly elevated levels of all biochemical makers. In histological analysis, a higher glomerulosclerosis index was observed in FGS/Nga than the two parental strains. RFM/Nga mice appeared to have slight sclerotic lesions of glomeruli, but no renal failure was observed in CBA/N mice. These results suggest that at least one mutant gene that causes the progression of renal lesion in FGS/Nga mice is derived from RFM/Nga. Key words: animal model, focal glomerular sclerosis (FGS), mouse, proteinuria function in human renal diseases [9,17]. Although it has been demonstrated by previous studies that the development of FGS is involved in immunologic injury, hemodynamic injury and metabolic abnormalities [1,6,7,10], the precise pathogenesis of FGS is still unclear.The FGS/Nga strain of mouse was introduced to

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Focal segmental glomerular sclerosis, a type of intractable chronic glomerulonephritis, is a stem cell disorder.

Cited by 71 publications

References 14 publications

Overexpression of Frat1 in transgenic mice leads to glomerulosclerosis and nephrotic syndrome, and provides direct evidence for the involvement of Frat1 in lymphoma progression

Overexpression of Frat1 in transgenic mice leads to glomerulosclerosis and nephrotic syndrome, and provides direct evidence for the involvement of Frat1 in lymphoma progression

Optimal protocol for total body irradiation for allogeneic bone marrow transplantation in mice

Changes of Renal Lesion-Related Parameters in FGS/Nga and the Parental Mouse Strains, CBA/N and RFM/Nga.

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