Heritable spina bifida in sheep: A potential model for fetal repair of myelomeningocele

J Pediatr Surg. 2020 Mar;55(3):475-481. doi: 10.1016/j.jpedsurg.2019.06.019. Epub 2019 Jun 29.

Abstract

Background/purpose: In 2004, a heritable occurrence of spina bifida was reported in sheep on a farm in the United States. We maintained and characterized the spina bifida phenotype in this flock to assess its potential as an alternative surgical model.

Methods: A breeding strategy was developed in which the sheep were crossed to maintain or increase the occurrence of spina bifida. Measurements and observations were recorded regarding lesion size, birthweight, ambulatory capacity, or urological function, and necropsies were performed on spina bifida afflicted lambs in conjunction with magnetic resonance imaging to determine the character of the spina bifida defects and assess the presence of Chiari-like malformations or hydrocephalus.

Results: The defects were observed to be more prevalent in ram lambs, and the rate of spina bifida per litter could be increased through backcrossing or by selection of a productive ewe breed. The lambs displayed a range of ambulatory and urological deficits which could be used to evaluate new fetal repair methodologies. Finally, affected lambs were shown to demonstrate severe Chiari malformations and hydrocephalus.

Conclusions: We have determined that use of these sheep as a natural source for spina bifida fetuses is feasible and could supplement the deficits of current sheep models for myelomeningocele repair.

Level of evidence: Level IV.

Keywords: Fetal sheep model; In utero surgery; Myelomeningocele; Spina bifida.

MeSH terms

  • Animals
  • Disease Models, Animal*
  • Female
  • Fetoscopy*
  • Meningomyelocele* / genetics
  • Meningomyelocele* / pathology
  • Meningomyelocele* / surgery
  • Pregnancy
  • Sheep
  • Spinal Dysraphism* / pathology
  • Spinal Dysraphism* / surgery