A mouse model of cardiac immunoglobulin light chain amyloidosis reveals insights into tissue accumulation and toxicity of amyloid fibrils

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 and Christophe Sirac ()
Additional contact information
Gemma Martinez-Rivas: University of Limoges, CRIBL lab, team 3 BioPIC
Maria Victoria Ayala: University of Limoges, CRIBL lab, team 3 BioPIC
Sebastien Bender: University of Limoges, CRIBL lab, team 3 BioPIC
Gilles Roussine Codo: University of Limoges, CRIBL lab, team 3 BioPIC
Weronika Karolina Swiderska: University of Limoges, CRIBL lab, team 3 BioPIC
Alessio Lampis: University of Limoges, CRIBL lab, team 3 BioPIC
Laura Pedroza: Centre for Medical Biotechnology
Melisa Merdanovic: Centre for Medical Biotechnology
Pierre Sicard: universityof Montpellier
Emilie Pinault: University of Limoges
Laurence Richard: University Hospital
Francesca Lavatelli: University of Pavia
Sofia Giorgetti: University of Pavia
Diana Canetti: University College London
Alexa Rinsant: University Hospital
Sihem Kaaki: University Hospital
Cécile Ory: University Hospital
Christelle Oblet: University of Limoges, CRIBL lab, team 3 BioPIC
Justine Pollet: University of Limoges, CRIBL lab, team 3 BioPIC
Eyad Naser: University Hospital Essen
Alexander Carpinteiro: University Hospital Essen
Muriel Roussel: University of Limoges, CRIBL lab, team 3 BioPIC
Vincent Javaugue: University of Limoges, CRIBL lab, team 3 BioPIC
Arnaud Jaccard: University of Limoges, CRIBL lab, team 3 BioPIC
Amélie Bonaud: University of Limoges, CRIBL lab, team 3 BioPIC
Laurent Delpy: University of Limoges, CRIBL lab, team 3 BioPIC
Michael Ehrmann: Centre for Medical Biotechnology
Frank Bridoux: University of Limoges, CRIBL lab, team 3 BioPIC
Christophe Sirac: University of Limoges, CRIBL lab, team 3 BioPIC

Nature Communications, 2025, vol. 16, issue 1, 1-16

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.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-58307-2 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-58307-2

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-58307-2

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().