The Mafb cleft-associated variant H131Q is not required for palatogenesis in the mouse.

Brian J Paul
Kristina Palmer, The Jackson Laboratory
Lindsey Rhea
Melissa Carlson
Jocelyn C Sharp, The Jackson Laboratory
C Herbert Pratt, The Jackson Laboratory
Stephen A. Murray, The Jackson Laboratory
Martine Dunnwald


BACKGROUND: Orofacial clefts (OFCs) are common birth defects with complex etiology. Genome wide association studies for OFC have identified SNPs in and near MAFB. MAFB is a transcription factor critical for structural development of digits, kidneys, skin, and brain. MAFB is also expressed in the craniofacial region. Previous sequencing of MAFB in a Filipino population revealed a novel missense variant significantly associated with an increased risk for OFC. This MAFB variant, leading to the amino acid change H131Q, was knocked into the mouse Mafb, resulting in the Mafb


CONCLUSIONS: Mafb is dispensable for murine palatogenesis in vivo, and the cleft-associated variant H131Q, despite its lack of morphogenic effect, altered the expression of Arhgap29 in a cell-dependent context.