Cloning of TgfβR1 and TgfβR2 and Likely Exclusion as Loci of Origin in a Rabbit Craniosynostotic Model.

Objective: To determine whether TgfβR1 or TgfβR2 cause the craniosynostotic phenotype in a rabbit model of nonsyndromic craniosynostosis.
Design: Full-length TgfβR1 and TgfβR2 cDNAs were sequenced and real-time reverse-transcription polymerase chain reaction (RT-PCR) was performed to measure TgfβR1 and TgfβR2 transcripts in sutural tissue from wild type (WT) and craniosynostotic (CS) rabbits. Single nucleotide polymorphisms (SNP) were identified within TgfβR1 and TgfβR2 and were assayed for segregation with disease phenotype in 22 craniosynostotic animals.
Results: No structural mutations in TgfβR1 and TgfβR2 were identified in the craniosynostotic rabbits. Real-time RT-PCR quantification of TgfβR1 and TgfβR2 mRNA showed no significant difference in TgfβR1 expression between CS and WT animals, while TgfβR2 showed 50% elevation in the CS animals compared to WT (P < .05). SNP analysis within the TgfβR1 and TgfβR2 genes suggested that neither locus is linked to the craniosynostotic phenotype because no allelic combination showed any specific correlation with disease phenotype for either TgfβR1 or TgfβR2.
Conclusions: Our data indicate that the craniosynostotic phenotype in this rabbit model does not arise from any structural mutation in TgfβR1 or TgfβR2, and SNP analysis also likely excludes these genes more broadly as the site of causative mutation.