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
StatePublished - Feb 2008

Fingerprint

Cleft Lip
lips
palate
embryo
Embryonic Structures
animal models
embryo (animal)
Palate
mice
Cleft Palate
Penetrance
penetrance
Inbred C57BL Mouse
mutation
genetic background
growth retardation
inbred lines
Mutation
Growth

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

Phenotypic variability and craniofacial dysmorphology : Increased shape variance in a mouse model for cleft lip. / Parsons, Trish E.; Kristensen, Erika; Hornung, Lynnette; Diewert, Virginia M.; Boyd, Steven K.; German, Rebecca Z.; Hallgrímsson, Benedikt.

In: Journal of Anatomy, Vol. 212, No. 2, 02.2008, p. 135-143.

Research output: Contribution to journalArticle

Parsons, TE, Kristensen, E, Hornung, L, Diewert, VM, Boyd, SK, German, RZ & Hallgrímsson, B 2008, 'Phenotypic variability and craniofacial dysmorphology: Increased shape variance in a mouse model for cleft lip', Journal of Anatomy, vol. 212, no. 2, pp. 135-143. https://doi.org/10.1111/j.1469-7580.2007.00845.x
Parsons, Trish E. ; Kristensen, Erika ; Hornung, Lynnette ; Diewert, Virginia M. ; Boyd, Steven K. ; German, Rebecca Z. ; Hallgrímsson, Benedikt. / Phenotypic variability and craniofacial dysmorphology : Increased shape variance in a mouse model for cleft lip. In: Journal of Anatomy. 2008 ; Vol. 212, No. 2. pp. 135-143.
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