biostudies-literatureMartinez-Rivas GLigue Contre le CancerFondation ARC pour la Recherche sur le CancerFondation ARC pour la Recherche sur le Cancer (ARC Foundation for Cancer Research)Agence Nationale de la RechercheFondation Française pour la recherche sur le Myelome et les Gammapathies monoclonalesConseil Régional Aquitaine (Aquitaine Regional Council)Agence pour la recherche contre le cancerFondazione Cariplo (Cariplo Foundation)Fondazione CariploDeutsche ForschungsgemeinschaftFondo Italiano per la Scienza (FIS 2021)Deutsche Forschungsgemeinschaft (German Research Foundation)Société française d'hématologieFondation pour la Recherche Médicale (Foundation for Medical Research in France)Agence Nationale de la Recherche (French National Research Agency)Fondation pour la Recherche MédicaleConseil Régional Aquitaine2992https://www.ebi.ac.uk/biostudies/studies/S-EPMC11950232biostudies-literatureUnknown16(1)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 Nature communicationsA mouse model of cardiac immunoglobulin light chain amyloidosis reveals insights into tissue accumulation and toxicity of amyloid fibrils.PMC11950232n.aCA 2420/2-1FRM-EQU2022030146152022-0578ANR-23-R4HC-0001-03ANR-21-CE17-0040-01EH 100/21-1Pinault EOblet CJaccard ADelpy LSirac CCodo GRMartinez-Rivas GRinsant ARichard LLavatelli FSicard PBridoux FCanetti DNaser EJavaugue VRoussel MPollet JAyala MVGiorgetti SEhrmann MBender SLampis ABonaud AMerdanovic MOry CPedroza LSwiderska WKCarpinteiro AKaaki SfalseA mouse model of cardiac immunoglobulin light chain amyloidosis reveals insights into tissue accumulation and toxicity of amyloid fibrils.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 2025-01-01T00:00:00Z2025 Mar2026-06-01T07:45:54.64Z2025-07-04T03:05:51.828ZS-EPMC119502324014827110.1038/s41467-025-58307-2