A mouse model of cardiac immunoglobulin light chain amyloidosis reveals insights into tissue accumulation and toxicity of amyloid fibrils
Abstract
Abstract Immunoglobulin light chain (LC) amyloidosis (AL) is one of the most common types of systemic amyloidosis but there is no reliable in vivo model for better understanding this disease. Here, we develop a transgenic mouse model producing a human AL LC. We show that the soluble full length LC is not toxic but a single injection of pre-formed amyloid fibrils or an unstable fragment of the LC leads to systemic amyloid deposits associated with early cardiac dysfunction. AL fibrils in mice are highly similar to that of human, arguing for a conserved mechanism of amyloid fibrils formation. Overall, this transgenic mice closely reproduces human cardiac AL amyloidosis and shows that a partial degradation of the LC is likely to initiate the formation of amyloid fibrils in vivo, which in turn leads to cardiac dysfunction. This is a valuable model for research on AL amyloidosis and preclinical evaluation of new therapies.
Article Details
Authors (29)
Gemma Martinez-Rivas
Maria Victoria Ayala
Sebastien Bender
Gilles Roussine Codo
Weronika Karolina Swiderska
Alessio Lampis
Laura Pedroza
Melisa Merdanovic
Pierre Sicard
Emilie Pinault
Laurence Richard
Francesca Lavatelli
Sofia Giorgetti
Diana Canetti
Alexa Rinsant
Sihem Kaaki
Cécile Ory
Christelle Oblet
Justine Pollet
Eyad Naser
Alexander Carpinteiro
Muriel Roussel
Vincent Javaugue
Arnaud Jaccard
Amélie Bonaud
Laurent Delpy
Michael Ehrmann
Frank Bridoux
Christophe Sirac