Phenotypic variability and craniofacial dysmorphology: Increased shape variance in a mouse model for cleft lip

Trish E. Parsons, Erika Kristensen, Lynnette Hornung, Virginia M. Diewert, Steven K. Boyd, Rebecca Z. German, Benedikt Hallgrímsson

Research output: Contribution to journalArticle

Abstract

Cleft lip and palate (CL/P), as is true of many craniofacial malformations in humans, is etiologically complex and highly variable in expression. A/WySn mice are an intriguing model for human CL/P because they develop this dysmorphology with a variable expression pattern, incomplete penetrance and frequent unilateral expression on a homogeneous genetic background. The developmental basis for this variation in expression is unknown, but of great significance for understanding such expression patterns in humans. As a step towards this goal, this study used three-dimensional geometric morphometric and novel high throughput morphometric techniques based on three-dimensional computed microtomography of mouse embryos to analyze craniofacial shape variation during primary palate formation. Our analysis confirmed previous findings based on two-dimensional analyses that the midface in A/WySn embryos, and the maxillary prominence in particular, is relatively reduced in size and appears to be developmentally delayed. In addition, we find that shape variance is increased in A/WySn embryos during primary palate formation compared to both C57BL/6J mice and the F1 crosses between these strains. If the reduction in midfacial growth caused by the Wnt9b hypomorphic mutation pushes A/WySn mice closer on average to the threshold for cleft lip formation, the elevated shape variance may explain why some, but not all, embryos develop the dysmorphology in a genetically homogeneous inbred line of mice.

Original languageEnglish (US)
Pages (from-to)135-143
Number of pages9
JournalJournal of Anatomy
Volume212
Issue number2
DOIs
Publication statusPublished - Feb 2008

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Keywords

  • Cleft lip and palate
  • Computed microtomography
  • Craniofacial development
  • Mouse embryos
  • Palate formation
  • Three-dimensional morphometrics

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Anatomy

Cite this

Parsons, T. E., Kristensen, E., Hornung, L., Diewert, V. M., Boyd, S. K., German, R. Z., & Hallgrímsson, B. (2008). Phenotypic variability and craniofacial dysmorphology: Increased shape variance in a mouse model for cleft lip. Journal of Anatomy, 212(2), 135-143. https://doi.org/10.1111/j.1469-7580.2007.00845.x