Figure 1. Mapping Selbst, an ASD-like phenotype of altered vocalization.

(A, B) Quantitative phenotype data (maximum peak frequency (A) and nesting score (B)) were used for linkage analyses (n = 17 WT, 24 Het, 3 Mut). Corresponding phenotypic data plotted against genotype at the Kdm5a mutation site are shown. Values are mean ± SEM ((A) ***p=0.0001; (B) time p<0.0001, genotype ***p=0.0003, time x genotype p=0.5155). Data were analyzed using ordinary one-way ANOVA (A) or two-way ANOVA (B), followed by Tukey's multiple comparisons test. (C) Representative spectrograms of vocalizations from WT, heterozygous (Het), and homozygous (Mut) mutant mice (n = 3 WT, 3 Het, 3 Mut). (D, E) Linkage plots showing P values calculated using the recessive model for the ultrasonic vocalization (USV) (D) and the nesting (E) phenotypes. The -log₁₀ P values (y axis) are plotted against the chromosomal positions of 60 mutations (x axis) identified in the G1 founder of the pedigree. Horizontal red and pink lines indicate thresholds of p=0.05 with or without Bonferroni correction, respectively.

Figure 1—figure supplement 1. Summary of the gene identification pipeline.

Related to Figure 1. Mutagenized G0 males were bred to WT C57BL/6J (B6) females (grey). G1 males, carrying mutations derived from the G0 male, were crossed to WT B6 females (grey). G2 females were then backcrossed to their G1 father to produce ~30–50 G3 mice with ENU-induced mutations. Asterisks represent mutations derived from the G0 male. Large asterisks indicate initial germline transmission. USVs were recorded from P4 G3 pups and nest building was assessed between P29 and P32.

Figure 1—figure supplement 2. KDM5A is ubiquitously expressed across tissues.

Related to Figure 1. (A) Human KDM5A tissue expression data publicly available from GTEx (Genotype-Tissue Expression Portal). (B) Kdm5a expression in the mouse brain, with inset showing high hippocampal expression. Data publicly available from the Allen Mouse Brain Atlas.