A rabbit model of human familial, nonsyndromic unicoronal suture synostosis I. Synostotic onset, pathology, and sutural growth patterns

Abstract

Poswillo has stated, "The more severe anomalies of the calvaria, such as plagiocephaly, Crouzon [syndrome], and Apert syndrome still defy explanation, in the absence of an appropriate animal system to study" (p. 207). This two-part study reviews data from a recently developed colony of New Zealand white rabbits with familial, nonsyndromic unilateral coronal suture synostosis. Part 1 presents pathological findings and compensatory sutural growth data from 109 normal rabbits and 82 craniosynostotic rabbits from this colony. Synostotic foci, onset, and progression were described in the calvariae from 102 staged (fetal days 21, 25, 27, 33; term = 30 days) fetuses (39 normal, 63 synostosed). Calvarial suture growth patterns from 10 to 126 days of age were assessed from serial radiographs obtained from 89 rabbits (70 normal rabbits and 19 rabbits with unicoronal suture synostosis) with amalgam bone marker implants. Perinatal results revealed that by fetal day 25 the synostotic focal point in synostotic rabbits consistently originated from the endocortical surface of the calvaria in the middle of the coronal suture at a presumed high-tension, interdigitating zone. Histological analysis revealed hyperostotic osteogenic fronts on the affected side compared with the unaffected side. Postnatal sutural growth data revealed a predictable pattern of plagiocephaly (contralateral coronal sutures growing more than ipsilateral sutures and ipsilateral frontonasal and anterior lambdoidal sutures growing more than contralateral sutures), which resulted in early cranial vault deformities and a double "S" shape torquing towards the affected side. The advantages and disadvantages of these rabbits as a model for human familial, nonsyndromic unicoronal suture synostosis are discussed, especially in light of recent cytokine and genetic findings from human craniosynostotic studies.

Spring-mediated skull expansion: overall effects in sutural and parasutural areas. An experimental study in rabbits

“…On the other hand, Mooney et al 12 and Putz et al 13 demonstrated changes in the cranial base and in intracranial pressure when suturectomies were performed in synostotic rabbits. This observation is essential for the understanding of skull behavior when subjected to expansion, since in addition to the expansor force exerted by the springs, the effect is strengthened by increased intracranial pressure, which enables ossification to take place once it is stabilized.…”

Postoperative Anti-Tgf-β2 Antibody Therapy Improves Intracranial Volume and Craniofacial Growth in Craniosynostotic Rabbits

“…5,9,76 The rabbits were randomly assigned to three groups as follows: group 1, suturectomy with no treatment, which served as the surgical control group (n = 9); group 2, suturectomy with nonspecific, control IgG antibody in a slow release collagen vehicle, which served as the antibody control group (n = 9); and group 3, suturectomy with anti-Tgf-b2 antibody in a slow release collagen vehicle, which served as the treatment group (n = 11). This study was reviewed and approved by the University of Pittsburgh, Institutional Animal Care and Use Committee.…”

Rescue of coronal suture fusion using transforming growth factor‐beta 3 (Tgf‐β3) in rabbits with delayed‐onset craniosynostosis

“…The present study was designed to test this hypothesis in a strain of rabbits with familial craniosynostosis (Mooney et al, 1994a(Mooney et al, , 1996a(Mooney et al, , 1998c. In particular, a number of clinical (Reddy et al, 1990;Hoffman and Reddy, 1991;Cohen et al, 1993;Cohen and MacLean, 2000) and animal (Mooney et al, 1994a(Mooney et al, , 1996a(Mooney et al, , 2002bBurrows et al, 1995;Losken et al, 1998Losken et al, , 1999) studies have identified and described a subset of craniosynostotic individuals with familial, nonsyndromic, delayed-onset (i.e., postgestational) craniosynostosis.…”