Table 3.

In vivo studies in animal models.

Study	Mutation type	Homozygous phenotype	Heterozygous phenotype	WT MYBPC3 protein levels compared to controls
Mouse Models
McConnell et al. (1999)[45] McConnell et al. (2001)[44] Vignier et al. (2009)[82] Fraysse et al. (2012)[19]	Truncation in exon 30	At 8–12 weeks: Fibrosis Diastolic dysfunction Dilated cardiomyopathy	At >125 weeks: LV wall hypertrophy No functional deficits	+/−: 89.9±8.5%
Harris et al. (2002)[27] Korte et al. (2003)[38]	Truncation removing exon 3–10	At 12 weeks: Ca2+ sensitivity ↓ Hypertrophy Diastolic dysfunction) accelerated cross-bridge cycling kinetics	No phenotype	+/−: no reduction −/−: no WT protein
Carrier et al. (2004)[13]	Transcription start site knock out	At ~14 weeks: Dilated cardiomyopathy Diastolic dysfunction Eccentric left ventricular hypertrophy	At 10–11 months: Asymmetric septal hypertrophy	At 10–11 mo +/−: ~75% −/−: 0%
Vignier et al. (2009)[82] Fraysse et al. (2012)[19] Gedicke-Hornung et al. (2013)[22] Mearini et al. (2014)[49]	Splice site (c.772G>A) multiple products. truncated and Δexon6	Ca2+ sensitivity ↑ Hypertrophy Diastolic dysfunction	Ca2+ sensitivity ↑ Diastolic dysfunction	At 60 weeks +/−: 79% of WT −/−: 10% of WT
Chen et al. (2012)[14]	Conditional Nonsense (tamoxifen induces deletion of exons 3–5)	Knockout induced at 12wkBy 20wk post tamoxifen (32wk): Myocyte hypertrophy Fibrosis		Less than 10% of vehicle controls by 8 weeks after tamoxifen treatment
Maine Coon Cat
Meurs et al. (2005)[52] Sampedrano et al. (2009)[12] Van Dijk et al. (2016)[77]	Ala31Pro	Hypertrophy Sudden death Diastolic dysfunction	Hypertrophy Longer lifespan than −/−	Allelic imbalance in +/− (WT >A31P). Total MYBPC3 expression unchanged in both +/− and −/−
Zebrafish
Chen et al. (2013)[15]	Knockdown using morpholinos against translation start site	At 72hr post fertilization, dose dependent increase in: Heart failure Ventricular wall thickness Atrial enlargement		Extent of knockdown not determined