Fig. 4: Kat6b overexpression rescues the anterior homeotic transformation seen in Kat6a–/– mice. | Nature Communications

Fig. 4: Kat6b overexpression rescues the anterior homeotic transformation seen in Kat6a–/– mice.

From: KAT6B overexpression rescues embryonic lethality in homozygous null KAT6A mice restoring vitality and normal lifespan

Fig. 4

a, b Alizarin red (bone) and Alcian blue (cartilage) stained skeletal preparations of N = 9 Kat6a+/+Kat6b+/+, 1 Kat6a–/–Kat6b+/+, 4 Kat6a–/–Tg(Kat6b) and 5 Kat6a+/+Tg(Kat6b) E18.5 foetuses with labelled cervical vertebrae (a) and sternum (b), arrow indicates abnormal rib attachment (b). Note that embryos homozygous for this allele of Kat6a rarely survive until E18.5. Representative images are shown. Representative images of RNA/RNA whole-mount situ hybridisation to detect Hoxa5 (c) and Hoxc5 (d) mRNA in Kat6a+/+Kat6b+/+, Kat6a–/–Kat6b+/+, Kat6a–/–Tg(Kat6b) and Kat6a+/+Tg(Kat6b) E10.5 embryos, with anterior expression boundary indicated. Note no staining using the sense control probe (n = 3 wild type embryos). The 3–4 most cranial somites are indicated by a dot (c, d). The anterior expression boundary of Hoxa5 is indicated by a stippled line (c). The distance between the anterior boundary of the Hoxc5 expression domain in the neural tube and the caudal boundary of the otic vesicle is indicated by a bracket (d). The distance was measured and is displayed in the bar graph in (d). Hoxa5 N = 3, Kat6a+/+Kat6b+/+, N = 3, Kat6a–/–Kat6b+/+, N = 3, Kat6a–/–Tg(Kat6b) and N = 3, Kat6a+/+Tg(Kat6b) were used. Hoxc5 N = 4, Kat6a+/+Kat6b+/+, N = 4, Kat6a–/–Kat6b+/+, N = 4, Kat6a–/–Tg(Kat6b) and N = 4, Kat6a+/+Tg(Kat6b) were used. This experiment was repeated a second time with each probe with N = 3 embryos per genotype. Data are presented as means ± s.e.m. and were analysed by one-way ANOVA with Tukey’s multiple comparison test. Circles in the bar graph (d) represent individual embryos. 1b, mandibular region of the first pharyngeal arch; 2, second pharyngeal arch; At, atlas = 1st cervical vertebra, C1; Ax, axis = 2nd cervical vertebra, C2; C1 to C7, 1st to 7th cervical vertebrae; C1’ to C8’, 1st to 8th abnormal Kat6a–/–Kat6b+/+ cervical vertebrae, whereby C8’ is supernumerary; E eye, FB forebrain, FL forelimb, HB hindbrain, He heart, HL hindlimb, M manubrium, MB midbrain, o otic vesicle, S sternebrae, T1 1st thoracic vertebra (rib bearing). Xp xiphoid process, Xs xiphisternum. Scale bar = 1 mm (a, b), 600 µm (c), 680 µm (d).

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