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Inbred Background Effects On Craniofacial Shape Dysmorphology In Mice With Spry Deletions
Author(s) -
Percival Christopher,
Mushegyan Vagan,
Tran DongKha,
Klein Ophir,
Hallgrímsson Benedikt
Publication year - 2015
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.29.1_supplement.697.2
Subject(s) - craniofacial , phenotype , heterozygote advantage , biology , genetics , gene deletion , craniofacial abnormality , inbred strain , gene , genotype , mutant
A mutation's effect on craniofacial phenotype is modulated by genetic background, but associated developmental interactions are not well understood. Our objective was to quantify the influence of three inbred backgrounds (FVB, 129, BL6) on the expression of craniofacial dysmorphology associated with Sprouty (Spry) 1, 2, and 4 deletions in mice. We quantified adult morphology with landmarks placed on micro‐computed tomography derived surfaces of heterozygote and homozygote knockouts, and unaffected littermates of each background. Within a background strain, mice with two deletions differ strongly from controls, including a visually identifiable rounded cranium and shortened face in Spry 2 homozygotes. Although not as extreme, heterozygotes significantly differ in shape from controls in many cases. Deletion effects are significantly different between background strains after correcting for shape differences in background controls, including a larger reduction of the nasal aperture associated with Spry1 deletion on 129 background versus FVB. Spry 4 deletion on FVB results in a more projected upper face associated with diastema teeth, while the effect of it on C57 is minimal. There are significant background effects on expression of craniofacial dysmorphology associated with Spry deletions, patterns of which can help illuminate how modifier genes can influence the effects of major genetic perturbations. Grant Funding Source: NIH (1R01‐DE021708, DP2‐OD007191, RO1‐DE021420, F30‐DE022482); NSERC (238992‐12); CIHR fellowship through ACHRI to CJP