Abstracts - Society for Developmental Biology

95
Program/Abstract # 290
A molecular and genetic approach to identifying a clinical rabbit craniosynostotic model and its relevance to
craniofacial development
Gallo, Phillip, University of Pittsburgh, Pittsburgh, United States; Cray Jr, James (Augusta, GA, United States); Durham,
Emily; Losee, Joseph; Mooney, Mark; Cooper, Gregory; Kathju, Sandeep (Pittsburgh, PA, United States)
Craniosynostosis, the premature fusion of the sutures of the cranial vault, clinically manifests with a range of severity from
subclinical phenotypes to severe cases, exhibiting increased intracranial pressure, severely altered head shape, and
premature death. Much of what is known about craniosynostosis is derived from studies in animal models and human
mutations in transforming growth factor beta receptors (TgfβRs), fibroblast growth factor receptors (FGFRs), Twist1, and
Msx2; these mutations, however, only account for 15 % of known craniosynostosis cases in humans. We have previously
described a colony of rabbits with an autosomal dominant heritable pattern of coronal suture synostosis. We undertook a
molecular analysis todetermine whether TgfβR1, TgfβR2, FGFR1, FGFR2 and / or Twist1 were the loci ofthe causative
mutation within our model system using single nucleotide polymorphisms (SNPs); SNPs were identified within our colony
through cDNA and genomic DNA cloning and sequencing. These SNPs were assayed for segregation with disease
phenotype in 22craniosynostotic animals. SNP analysis within the TgfβR1, TgfβR2, FGFR1, FGFR2, and Twist1 genes
indicated that none of these loci are linked to the craniosynostotic phenotype as no allelic combination showed any specific
correlation with disease phenotype. As no SNP arrays exist for rabbits, we sought a molecular /bioinformatics method to
create a SNP map in rabbits with the ultimate goal of mapping the defect in our rabbit colony. Utilizing recent
advancements in next generation sequencing, we used the recently published restriction site associated DNA sequencing
technique (RADsequencing) to identify SNPs in our rabbit genome compared to wild type animals maintained separately
from our breeding colony. This analysis described over 60,000 SNPs within our animals that can be mapped to the lowdensity
rabbit genome currently available. Subsequent bioinformatics analysis identified approximately 6,000 SNPs that
map to the craniosynostotic colony, an important first step in identifying genes that segregate with the craniosynostosis
phenotype for future mapping purposes. Since we have already ruled out five genes known to be involved in cranio
synostosis, this well-established clinical model provides a unique opportunity to decipher the molecular pathways
functioning in craniofacial development.
Program/Abstract # 291
Effect of low molecular weight chitosan oligosaccharides reduces pulmonary fibrosis in a Bleomycin mouse model
Hong, Heejoo, Gachon University, Inchon, Korea, Republic of; Kim, Ji sun; Kim, Sung Won; Park, Soo Jong; Park,
Cheol Ho; Park, Jae Kweon; Hwang, You Hin; Kim, Dae Yong (Gachon University, Inchon, Republic of Korea)
In human, idiopathic pulmonary fibrosis is characterized by alveolar epithelial cell injury and lose its functions. This
disease leads to impairment of gas exchange and pulmonary function because of the loss of lung elasticity and alveolar
surface area. Bleomycin is limited because it produces dose-dependent pulmonary toxicity which induces interstitial
pulmonary fibrosis. Low molecular weight chitosan oligosaccharides (LM-COS) has effects of anti-inflammatory. LM-
COS (