The Mafb cleft-associated variant H131Q is not required for palatogenesis in the mouse
| Autor: | Kristina Palmer, Jocelyn C. Sharp, Melissa Carlson, C. Herbert Pratt, Stephen A. Murray, Martine Dunnwald, Lindsey Rhea, Brian J. Paul |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Population MafB Transcription Factor Context (language use) Genome-wide association study Mice Transgenic Biology medicine.disease_cause Polymorphism Single Nucleotide Article 03 medical and health sciences Mice 0302 clinical medicine Keratin medicine Missense mutation Animals Genetic Predisposition to Disease education Transcription factor Alleles chemistry.chemical_classification Mutation education.field_of_study Palate Cell biology Cleft Palate 030104 developmental biology chemistry MAFB 030217 neurology & neurosurgery Developmental Biology |
| Zdroj: | Dev Dyn |
| Popis: | 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 MafbH131Q allele. The MafbH131Q construct was engineered to allow for deletion of Mafb ("Mafbdel "). Results Mafbdel/del animals died shortly after birth. Conversely, MafbH131Q/H131Q mice survived into adulthood at Mendelian ratios. Mafbdel/del and MafbH131Q/H131Q heads exhibited normal macroscopic and histological appearance at all embryonic time points evaluated. The periderm was intact based on expression of keratin 6, p63, and E-cadherin. Despite no effect on craniofacial morphogenesis, H131Q inhibited the Mafb-dependent promoter activation of Arhgap29 in palatal mesenchymal, but not ectodermal-derived epithelial cells in a luciferase assay. 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. This article is protected by copyright. All rights reserved. |
| Databáze: | OpenAIRE |
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