The effects of Tbx15 and Pax1 on facial and other physical morphology in mice.

ABSTRACT: DNA variants in or close to the human TBX15 and PAX1 genes have been repeatedly associated with facial morphology in independent genome-wide association studies, while their functional roles in determining facial morphology remain to be understood. We generated Tbx15 knockout (Tbx15 ^-/-) and Pax1 knockout (Pax1 ^-/-) mice by applying the one-step CRISPR/Cas9 method. A total of 75 adult mice were used for subsequent phenotype analysis, including 38 Tbx15 mice (10 homozygous Tbx15 ^-/-, 18 heterozygous Tbx15 ^+/-, 10 wild-type Tbx15 ^+/+ WT littermates) and 37 Pax1 mice (12 homozygous Pax1 ^-/-, 15 heterozygous Pax1 ^+/-, 10 Pax1 ^+/+ WT littermates). Facial and other physical morphological phenotypes were obtained from three-dimensional (3D) images acquired with the HandySCAN BLACK scanner. Compared to WT littermates, the Tbx15 ^-/- mutant mice had significantly shorter faces (p = 1.08E-8, R² = 0.61) and their ears were in a significantly lower position (p = 3.54E-8, R² = 0.62) manifesting a "droopy ear" characteristic. Besides these face alternations, Tbx15 ^-/- mutant mice displayed significantly lower weight as well as shorter body and limb length. Pax1 ^-/- mutant mice showed significantly longer noses (p = 1.14E-5, R² = 0.46) relative to WT littermates, but otherwise displayed less obvious morphological alterations than Tbx15 ^-/- mutant mice did. We provide the first direct functional evidence that two well-known and replicated human face genes, Tbx15 and Pax1, impact facial and other body morphology in mice. The general agreement between our findings in knock-out mice with those from previous GWASs suggests that the functional evidence we established here in mice may also be relevant in humans.

SUBMITTER: Qian Y 

PROVIDER: S-EPMC8664010 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature