On 2017 Dec 06, Alexander Kraev commented:

This is an interesting case of active nescience, because both authors were aware, even before their work started, of the fact that the PLN transgenic strain they used had a peculiar genomic structure that resulted in the presence of two resident wildtype PLN gene copies and 13 transgenic mutant (R9C) PLN gene copies under the control of alpha-MHC promoter. This situation can never, even theoretically, occur in a human patient (https://doi.org/10.1101/075671). Yet, they chose to compare it to another transgenic strain, expressing another gene with the same promoter cassette, wherein the transgene structure and genomic location are unknown. The authors state that "Although these mice are DCM models, their etiology are different from each other", which is based on the assumption that different genes are used in the two transgenes. The original descriptions of the transgenes both lack data on transgene localization and also lack the minimally necessary controls, such as an analysis of two or more transgenic lines produced with the same DNA construct. The readers should interpret the data in this paper with extreme caution, since some or all of the "universality in failing hearts" found between the two strains may stem from the use of the common expression cassette, and/or its genomic location. However, if these data are ever validated by the use of a more advanced transgenic method, this paper would serve as a good reference of the extent of conceptual misdirection the lack of transgene genomic characterization can induce.

On 2017 Dec 06, Alexander Kraev commented:

This is an interesting case of active nescience, because both authors were aware, even before their work started, of the fact that the PLN transgenic strain they used had a peculiar genomic structure that resulted in the presence of two resident wildtype PLN gene copies and 13 transgenic mutant (R9C) PLN gene copies under the control of alpha-MHC promoter. This situation can never, even theoretically, occur in a human patient (https://doi.org/10.1101/075671). Yet, they chose to compare it to another transgenic strain, expressing another gene with the same promoter cassette, wherein the transgene structure and genomic location are unknown. The authors state that "Although these mice are DCM models, their etiology are different from each other", which is based on the assumption that different genes are used in the two transgenes. The original descriptions of the transgenes both lack data on transgene localization and also lack the minimally necessary controls, such as an analysis of two or more transgenic lines produced with the same DNA construct. The readers should interpret the data in this paper with extreme caution, since some or all of the "universality in failing hearts" found between the two strains may stem from the use of the common expression cassette, and/or its genomic location. However, if these data are ever validated by the use of a more advanced transgenic method, this paper would serve as a good reference of the extent of conceptual misdirection the lack of transgene genomic characterization can induce.