Progressive phenotype and nuclear accumulation of an amino-terminal cleavage fragment in a transgenic mouse model with inducible expression of full-length mutant huntingtin

2006 ◽  
Vol 21 (2) ◽  
pp. 381-391 ◽  
Author(s):  
Yuji Tanaka ◽  
Shuichi Igarashi ◽  
Masayuki Nakamura ◽  
Juliette Gafni ◽  
Cameron Torcassi ◽  
...  
Keyword(s):  
Mouse Model ◽  
Transgenic Mouse ◽  
Transgenic Mouse Model ◽  
Inducible Expression ◽  
Full Length ◽  
Nuclear Accumulation ◽  
Mutant Huntingtin ◽  
Cleavage Fragment ◽  
Amino Terminal

scholarly journals Transgenic Mouse Model Expressing the Caspase 6 Fragment of Mutant Huntingtin

2012 ◽  
Vol 32 (1) ◽  
pp. 183-193 ◽  
Author(s):  
E. Waldron-Roby ◽  
T. Ratovitski ◽  
X. Wang ◽  
M. Jiang ◽  
E. Watkin ◽  
...  
Keyword(s):  
Mouse Model ◽  
Transgenic Mouse ◽  
Transgenic Mouse Model ◽  
Mutant Huntingtin ◽  
Caspase 6

scholarly journals Nuclear Accumulation of Truncated Atrophin-1 Fragments in a Transgenic Mouse Model of DRPLA

Neuron ◽  
1999 ◽  
Vol 24 (1) ◽  
pp. 275-286 ◽  
Author(s):  
Gabriele Schilling ◽  
Jonathan D. Wood ◽  
Kui Duan ◽  
Hilda H. Slunt ◽  
Vicky Gonzales ◽  
...  
Keyword(s):  
Mouse Model ◽  
Transgenic Mouse ◽  
Transgenic Mouse Model ◽  
Nuclear Accumulation

PP-22 A transgenic mouse model with inducible expression of the tyrosinase gene

2003 ◽  
Vol 16 (5) ◽  
pp. 600-600 ◽  
Author(s):  
A. Lavado ◽  
E. Gimenez ◽  
P. Giraldo ◽  
P. Cozar ◽  
G. Jeffery ◽  
...  
Keyword(s):  
Mouse Model ◽  
Transgenic Mouse ◽  
Transgenic Mouse Model ◽  
Inducible Expression ◽  
Tyrosinase Gene

scholarly journals A Transgenic Mouse Model of Cardiac AL Amyloidosis

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1592-1592
Author(s):  
Gemma Martinez-Rivas ◽  
Maria Ayala ◽  
Sebastien Bender ◽  
Murielle Roussel ◽  
Arnaud Jaccard ◽  
...  
Keyword(s):  
Mouse Model ◽  
Board Of Directors ◽  
Transgenic Mouse ◽  
Amyloid Fibrils ◽  
Plasma Cells ◽  
Transgenic Mouse Model ◽  
Full Length ◽  
Al Amyloidosis ◽  
Advisory Committees

Abstract Background: AL amyloidosis is the most frequent type of amyloidosis caused by the deposition in tissues of fibrillar aggregates composed of an abnormal immunoglobulin (Ig) light chain (LC) and leading to organ dysfunction. The most frequent and severe forms involve kidney and heart. Research on this disease suffers from the lack of reliable animal models, that could allow a better understanding of the disease and the design of new therapeutic strategies. In the present study, we aimed at reproducing AL amyloidosis in a mouse model. Methods: We developed an original transgenic approach using an insertion of a human pathogenic LC gene in the endogenous mouse kappa locus, such as the LC is produced by the naturally Ig producing B and plasma cells. Then, to avoid the association of human LCs with endogenous murine HCs, we backcrossed this strain with the DH-LMP2A mice, characterized by a high number of plasma cells devoid of endogenous HC. This strategy leads to a production of the human free LC similar or higher than in patients and proved efficient to reproduce in mice several monoclonal gammopathies of clinical significance (MGCS) (Fig.1A). Results: Despite strong LC production (Fig.1B), mice did not naturally develop AL amyloidosis. In vitro, the full length LC was resistant to amyloid formation at physiological conditions but the variable domain (IGLV6) showed high propensity to form fibrils. A single injection of amyloid fibrils and/or seeds, obtained from the variable domain (VL) of the human LC gene, led to amyloid deposits starting at 1 month post-injection, especially in the heart, spleen, liver and, to a lesser extent, in the kidney (Fig.1C). We confirmed that the deposits contain the full-length human LCs, which elongate VL fibrils in vivo (Fig.1D). Conclusions: This is, to our knowledge, the first transgenic mouse model of AL amyloidosis closely reproducing human lesions, especially in heart. Further studies are needed to better understand the early biochemical events leading to AL amyloidosis in vivo, but this model already shows that a partial degradation of the LC is likely required to initiate amyloid fibrils and that once seeded, the full length LC can elongate these fibrils. This mouse model opens new perspectives to better understand the toxicity of amyloid LC, their involvements in different biological processes and organ dysfunction and of course, to test new therapeutic approaches. Figure 1 Figure 1. Disclosures Roussel: Takeda: Consultancy; Janssen: Membership on an entity's Board of Directors or advisory committees; GSK: Honoraria; BMS: Honoraria; Amgen: Consultancy. Jaccard: Janssen: Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria; Abbvie: Honoraria. Bridoux: Janssen: Consultancy; AstraZeneca: Consultancy, Speakers Bureau. Sirac: Attralus, Inc: Patents & Royalties, Research Funding.

scholarly journals Generation of a transgenic mouse model with chondrocyte-specific and tamoxifen-inducible expression of Cre recombinase

genesis ◽  
2007 ◽  
Vol 45 (1) ◽  
pp. 44-50 ◽  
Author(s):  
Mo Chen ◽  
Alexander C. Lichtler ◽  
Tzong-Jen Sheu ◽  
Chao Xie ◽  
Xinping Zhang ◽  
...  
Keyword(s):  
Mouse Model ◽  
Transgenic Mouse ◽  
Cre Recombinase ◽  
Transgenic Mouse Model ◽  
Inducible Expression
Sign in / Sign up

Export Citation Format

Share Document