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. 2021 Mar 11;11:5659. doi: 10.1038/s41598-021-84894-3

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© The Author(s) 2021

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Comparison of Atp7b mutant mice suggests potential markers and modifying factors. (a) Unsupervised clustering of protein profiles from the dataset # 2 (see methods) was done using Spotfire DecisionSite with Functional Genomics v9.1.2 (https://edelivery.tibco.com/storefront/eval/tibco-spotfire-decisionsite-for-functional-genomics/prod10196.html) and presented as a heat map; the map illustrates marked differences between the wt animals and Atp7b^−/− global knockouts and presence of similarly changed proteins in Atp7b^−/− mice on different genetic backgrounds heat map (b) The most significantly dysregulated proteins (|S|= 6, p value < 0.05) detected in all Atp7b-mutant mice. Green color highlights protein with changes in abundance that reflect the extent of liver pathology; blue indicate proteins that are oppositely changed in the hepatocyte-specific and global knockouts; (c) Upregulation of metallothioneins MT1 and MT2 in Atp7b-deficient strains. One-way ANOVA and a two-tail t-test for individual pairs (shown) were used (*p value ≤ 0.05, **p value ≤ 0.01, ***p value ≤ 0.001) and yielded same conclusions. “Ctrl” indicates either Atp7b^+/+ or Atp7b ^+/- animals; “M”—males; “F”—females. (d) Left: Correlation between the abundance of metallothioneins MT1 and MT2 in individual Atp7b^−/− animals and the number of proteins in their liver proteome changed more than1.5-fold compared to the averaged wild-type on the same genetic background. Right: Correlation between abundances of MT1 and MT2 and levels of glucokinase in individual Atp7b^−/− animals. “NI” indicates a normalized protein intensity.