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The effects of Gtf2i and Gtf2ird1 mutations on the skull in Williams‐Beuren Syndrome
Author(s) -
Hill Cheryl A.,
Kirkland Nicole M.,
Kopp Nathan D.,
Dougherty Joseph D.
Publication year - 2020
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.2020.34.s1.06195
Subject(s) - craniofacial , phenotype , skull , biology , genetics , williams syndrome , wild type , gene , craniofacial abnormality , anatomy , mutant , neuroscience , cognition
Williams‐Beuren syndrome (WBS) is a neurodevelopmental disorder caused by a 1–8 Mbp deletion on chromosome 7. In addition to hypersocial personalities and visuospatial changes, individuals with WBS also show changes in cardiovascular and craniofacial phenotypes. GTF2I AND GTF2IRD1 have been implicated in producing the changes seen in the craniofacial phenotype. The purpose of this study is to determine if Gtf2ird1 and Gtf2i interact to produce craniofacial features associated with WBS in mouse models. Using CRISPR/CAS9 technology, we developed two new mouse models loss‐of‐function mutations in both Gtf2ird1 and Gtf2i and wildtype littermates. The study sample includes computed tomography scans acquired from the skulls of mice with differing number of mutations in these genes and their wildtype littermates (N=119). Three‐dimensional landmark coordinate data were collected from scans of the skull and analyzed using geometric morphometrics. Skulls of mice with only one loss‐of‐function mutation in Gtf2ird1 were not different from wildtype littermates, while mutations in both Gtf2i and Gtf2ird1 show variable results across the two models. Our results indicate that loss‐of‐function mutations in Gtf2ird1 and Gtf2i interact in nuanced ways to affect the craniofacial structure in these mouse models for Williams‐Beuren syndrome. Varying protein expressions within these mice, interactions with other genes in the deleted region of chromosome 7 and other factors lead to changes in the craniofacial phenotype seen in Williams‐Beuren syndrome. Support or Funding Information 5R01MH107515‐03 to JDD, NSF fellowship DGE‐1745038 to NDK.