Skip to main content
. Author manuscript; available in PMC: 2020 Apr 9.
Published in final edited form as: Circulation. 2019 Apr 9;139(15):1813–1827. doi: 10.1161/CIRCULATIONAHA.118.037588

Figure 1. Failure to thrive and early lethality of titin knockouts deficient in titin (E2) versus titin’s M-band region (M1/2).

Figure 1.

A) Schematic illustration of titin’s first and last exons of the wildtype, exon 2 (E2) and M-band knockout (M1/2). Triangles indicate lox sites (locus of X(cross)-over). B) E2-KO and M1/2-KO mice die from 10 and 15 days of life, respectively with no survivors beyond day 40, while control mice (CTRL) survive. C) Compared to the respective control without the Cre recombinase, E2-KO and M1/2-KO mice appear smaller and weaker at 35 days. Differences in posture include kyphosis and outward extended hindlimbs. D) Body weight does not increase from week two after birth and stays at ~10 g for either knockout model. E) Muscle strength as determined in an inverted screen grid holding test is severely reduced in E2 and M1/2-KO mice and precedes the reduced weight gain and muscle atrophy. Log rank (Mantel Cox) test, *** p < 0.001, n = 23 control, n = 14 for E2, n = 9 for M1/2 knockout (B). Repeated measure 2-way ANOVA with Bonferroni post-test, ** p < 0.01; *** p < 0.001, n = 12 controls, n = 6 per knockout (D, E).