Gilbert James R, Taylor Gwen M, Losee Joseph E, Mooney Mark P, Cooper Gregory M
1 Department of Plastic Surgery, Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, PA, USA.
2 Department of Pediatrics, Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, PA, USA.
Cleft Palate Craniofac J. 2018 Mar;55(3):375-382. doi: 10.1177/1055665617739001. Epub 2017 Dec 18.
Craniosynostosis (CS) involves the premature fusion of one or more cranial sutures. The etiology of CS is complex and mutations in more than 50 distinct genes have been causally linked to the disorder. Many of the genes that have been associated with CS in humans play an essential role in tissue patterning and early craniofacial development. Among these genes are members of the Hedgehog (HH) and Notch signal transduction pathways, including the GLI family member Gli3, Indian Hedgehog ( Ihh), the RAS oncogene family member Rab23, and the Notch ligand JAGGED1 ( Jag1). We have previously described a colony of rabbits with a heritable pattern of coronal suture synostosis, although the genetic basis for synostosis within this model remains unknown. The present study was performed to determine if coding errors in Gli3, Ihh, Rab23, or Jag1 could be causally linked to craniosynostosis in this unique animal model.
Sequencing of cDNA templates was performed using samples obtained from wild-type and craniosynostotic rabbits.
Several nucleotide polymorphisms were identified in Gli3, Ihh, and Rab23, although these variants failed to segregate by phenotype. No nucleotide polymorphisms were identified in Jag1.
These data indicate that the causal locus for heritable craniosynostosis in this rabbit model is not located within the protein coding regions of Gli3, Ihh, Rab23, or Jag1.
颅缝早闭（CS）涉及一条或多条颅缝的过早融合。CS的病因复杂，50多个不同基因的突变与该疾病存在因果关系。许多与人类CS相关的基因在组织模式形成和早期颅面发育中起着至关重要的作用。这些基因包括刺猬（HH）和Notch信号转导通路的成员，如GLI家族成员Gli3、印度刺猬因子（Ihh）、RAS癌基因家族成员Rab23以及Notch配体JAGGED1（Jag1）。我们之前描述过一群具有遗传性冠状缝早闭模式的兔子，尽管该模型中早闭的遗传基础尚不清楚。本研究旨在确定Gli3、Ihh、Rab23或Jag1中的编码错误是否与这种独特动物模型中的颅缝早闭存在因果关系。
使用从野生型和颅缝早闭兔子获得的样本对cDNA模板进行测序。
在Gli3、Ihh和Rab23中鉴定出了几个核苷酸多态性，尽管这些变异未能按表型分离。在Jag1中未鉴定出核苷酸多态性。
这些数据表明，该兔子模型中遗传性颅缝早闭的致病基因座不在Gli3、Ihh、Rab23或Jag1的蛋白质编码区域内。
