Fig. 7: Disease-associated mutations impairs mouse USVs by relieving the transcriptional repression of TCF7L2.
a Gene structure of TCF7L2 and human mutations found in patients (PMID: 25363768, 25533962, 28191889, and 34003604). b–e Generation of Tcf7l2 knockin mouse lines carrying disease-associated mutations. TCF7L2 expression in P7 midbrains with indicated genotypes (d, f). e, g The syllable numbers, mean frequency, syllable duration, and peak syllable amplitude measured at P7 with indicated genotypes. h Protein sequence alignment of TCF7L2 HMG domain. Human TCF7L2 (NM_001198528) were employed for positioning. Disease-associated mutations include: 1) our ENU-induced Y337H mutation colored in red; 2) mutations described in previous studies are colored in black (PMID: 25363768) and blue (PMID:34003604), respectively. i Transcriptional repression of dnTCF7L2 (DN), which lacks of CBD (beta-catenin binding domain), was relieved by the disease-associated mutations shown in h. Previously reported TOPFlash luciferase reporter (PMID: 9065401) was employed for the measurement. FL, full-length TCF7L2. Renilla luciferase activity was used for normalization. The value are presented as mean ± SD. N.S., no significant difference, **p < 0.01, ***p < 0.001, t-test or ANOVA, SPSS. In d, i, n = 3; in f, n = 4; in e, g, +/+ (n = 10), Tcf7l2c.932+1G>A/+ (n = 8), and Tcf7l2R384X/+ (n = 10).
