Mutations of GADD45G in rabbits cause cleft lip by the disorder of proliferation, apoptosis and epithelial-mesenchymal transition (EMT).
The cleft lip with or without cleft palate (CL/P) is one of the most common congenital defects in humans. Genome-wide association studies (GWAS) have been widely used for identifying candidate genes, and different genes or chromosomal regions have shown strong evidence for the presence of causal genes in CL/P. To date, two independent GWAS have identified GADD45G as influencing risk for CL/P. However, there is no animal model evidence about GADD45G related to CL/P. Here, we reported the generation of a novel GADD45G mutated rabbit model by CRISPR/Cas9 and CRISPR-based BE4-Gam systems. The homozygous (GADD45G-/-) while not heterozygous (GADD45G+/-) pups died after birth due to severe craniofacial defects of unilateral or bilateral cleft lip (CL). Moreover, the disorder of proliferation, apoptosis and epithelial-mesenchymal transition (EMT) were also determined in the medial and lateral nasal processes (MNP and LNP) of the embryonic day 13 (E13) GADD45G-/- rabbits, which compared with the normal wild type (WT) rabbits. Thus, our study confirmed for the first time that loss of GADD45G lead to CL at the animal level and provided new insights into the crucial role of GADD45G for upper lip formation and fusion.
['Lu|Yi|Y|', 'Liang|Mingming|M|', 'Zhang|Quanjun|Q|', 'Liu|Zhiquan|Z|', 'Song|Yuning|Y|', 'Lai|Liangxue|L|', 'Li|Zhanjun|Z|']
D000818:Animals D017209:Apoptosis D064113:CRISPR-Cas Systems D049109:Cell Proliferation D002971:Cleft Lip D004622:Embryo, Mammalian D047108:Embryonic Development D058750:Epithelial-Mesenchymal Transition D055786:Gene Knockout Techniques D006720:Homozygote D047908:Intracellular Signaling Peptides and Proteins D008046:Lip D009154:Mutation D017434:Protein Structure, Tertiary D011817:Rabbits
GADD45G Rabbit Cleft lip CRISPR/Cas9 BE4-Gam