Cloning of Tgf[Beta]R1 and Tgf[Beta]R2 and Likely Exclusion as Loci of Origin in a Rabbit Craniosynostotic Model

• Published in: The Cleft palate-craniofacial journal 2014-01, Vol.51 (1), p.56
• Main Authors: Gallo, Phillip H, Durham, Emily L, Losee, Joseph E, Mooney, Mark P, Cooper, Gregory M, Kathju, Sandeep
• Format: Article
• Language: English
• Subjects: Congenital diseases; Gene expression; Genes; Mutation; Rabbits; Studies
• ISSN: 1055-6656; 1545-1569

Objective: To determine whether Tgf[beta]R1 or Tgf[beta]R2 cause the craniosynostotic phenotype in a rabbit model of nonsyndromic craniosynostosis. Design: Full-length Tgf[beta]R1 and Tgf[beta]R2 cDNAs were sequenced and real-time reverse-transcription polymerase chain reaction (RT-PCR) was performed to measure Tgf[beta]R1 and Tgf[beta]R2 transcripts in sutural tissue from wild type (WT) and craniosynostotic (CS) rabbits. Single nucleotide polymorphisms (SNP) were identified within Tgf[beta]R1 and Tgf[beta]R2 and were assayed for segregation with disease phenotype in 22 craniosynostotic animals. Results: No structural mutations in Tgf[beta]R1 and Tgf[beta]R2 were identified in the craniosynostotic rabbits. Real-time RT-PCR quantification of Tgf[beta]R1 and Tgf[beta]R2 mRNA showed no significant difference in Tgf[beta]R1 expression between CS and WT animals, while Tgf[beta]R2 showed 50% elevation in the CS animals compared to WT (P < .05). SNP analysis within the Tgf[beta]R1 and Tgf[beta]R2 genes suggested that neither locus is linked to the craniosynostotic phenotype because no allelic combination showed any specific correlation with disease phenotype for either Tgf[beta]R1 or Tgf[beta]R2. Conclusions: Our data indicate that the craniosynostotic phenotype in this rabbit model does not arise from any structural mutation in Tgf[beta]R1 or Tgf[beta]R2, and SNP analysis also likely excludes these genes more broadly as the site of causative mutation.