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Patient‐derived MAFB Missense Mutation Is Associated with Cleft Palate in Mice
Author(s) -
Paul Brian J.,
Palmer Kristina,
Padilla Crystal,
Sharp Jocelyn C.,
Pratt C Herbert,
Murray Stephen A.,
Dunnwald Martine
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.776.6
Subject(s) - missense mutation , biology , craniofacial , genetics , exon , mutation , gene
Non‐syndromic cleft lip with or without cleft palate (NSCL/P) is a common birth defect with complex etiology. Amongst the numerous genes involved, mutations in MAFB (MAF BZIP Transcription Factor B) were recently associated with increased risk for NSCL/P. MAFB , a single‐exon gene of 3.3kb, encodes the protein MAFB, which is a transcription factor expressed in the craniofacial region at time points critical for palatal development. Previous sequencing of MAFB in cases revealed a novel missense mutation which was significantly associated with an increased risk of NSCL/P. This patient‐derived MAFB mutation, leading to the amino acid change H131Q, was knocked‐into the mouse Mafb , resulting in the allele Mafb H131Q . In contrast to Mafb nulls, which die shortly after birth, Mafb H131Q mice survived into adulthood at Mendelian ratios. Mafb H131Q embryos were harvested for serial sectioning and histological characterization at time points critical for craniofacial development. One Mafb H131Q/H131Q animal at embryonic day (e) 18.5 (N = 12) exhibited highly abnormal craniofacial morphology that included a cleft palate and shortened snout. At e13.5, our preliminary data indicate the presence of mild oral adhesions in Mafb H131Q/+ and Mafb H131Q/H131Q mice that were absent in wild type animals. However, immunofluorescence for periderm markers did not indicate altered expression of keratin 6 and keratin 17. These data demonstrate functional significance of the patient‐derived H131Q mutation and its role in the etiology of NSCL/P. Support or Funding Information MD ‐ NIH/NIAMS AR067739. Additional partial financial support was provided by a grant from the NIH R37DE08559 and by the FaceBase consortium (grants DE020052 and DE020057) CP ‐ Iowa Biosciences Academy, funded by NIH/NIGMS R25GM058939, the University of Iowa (UI) Office of the Vice President for Research, and the UI Chief Diversity Office. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .