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J Pediatr Surg. 2019 Jun 29. pii: S0022-3468(19)30446-4. doi: 10.1016/j.jpedsurg.2019.06.019. [Epub ahead of print]

Heritable Spina Bifida in Sheep: A Potential Model for Fetal Repair of Myelomeningocele.

Author information

1
Center for Precision Environmental Health, Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030; Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, TX 78712. Electronic address: John.Steele@bcm.edu.
2
Bayliss Sheep Farm, Rushsylvania, OH 43347. Electronic address: skbrn52@embarqmail.com.
3
Bayliss Sheep Farm, Rushsylvania, OH 43347. Electronic address: baybld@embarqmail.com.
4
Center for Precision Environmental Health, Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030. Electronic address: Ying.Lin@bcm.edu.
5
Center for Precision Environmental Health, Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030. Electronic address: Bogdan.Wlodarczyk@bcm.edu.
6
Center for Precision Environmental Health, Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030. Electronic address: Robert.Cabrera@bcm.edu.
7
Division of Laboratory Animal Resources, Duke University Medical Center, Durham, NC 27710. Electronic address: yohannes.asfaw@duke.edu.
8
Department of Pathology, Duke University Medical Center, Durham, NC 27710. Electronic address: thomas.cummings@duke.edu.
9
Center for Precision Environmental Health, Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030. Electronic address: Richard.Finnell@bcm.edu.
10
Department of Neurosurgery/Pediatric Neurosurgery, Dell Medical School, Dell Children's Medical Center, Austin, TX 78712. Electronic address: timothy.george@austin.utexas.edu.

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

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