John W Steele1, Sharon Bayliss2, John Bayliss3, Ying Linda Lin4, Bogdan J Wlodarczyk5, Robert M Cabrera6, Yohannes G Asfaw7, Thomas J Cummings8, Richard H Finnell9, Timothy M George10. 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.
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.
Authors: Jose L Peiro; Cesar G Fontecha; Rodrigo Ruano; Marielle Esteves; Carla Fonseca; Mario Marotta; Sina Haeri; Michael A Belfort Journal: Surg Endosc Date: 2013-05-14 Impact factor: 4.584
Authors: M Meuli; C Meuli-Simmen; G M Hutchins; C D Yingling; K M Hoffman; M R Harrison; N S Adzick Journal: Nat Med Date: 1995-04 Impact factor: 53.440
Authors: Sarah Bouchard; Marcus G Davey; Natalie E Rintoul; Danielle S Walsh; Lucy B Rorke; N Scott Adzick Journal: J Pediatr Surg Date: 2003-03 Impact factor: 2.545
Authors: Ramesha Papanna; Lovepreet K Mann; Saul Snowise; Yisel Morales; Sanjay P Prabhu; Scheffer C G Tseng; Raymond Grill; Stephen Fletcher; Kenneth J Moise Journal: AJP Rep Date: 2016-07
Authors: Paul Wolujewicz; John W Steele; Julia A Kaltschmidt; Richard H Finnell; Margaret Elizabeth Ross Journal: Genesis Date: 2021-10-29 Impact factor: 2.487
Authors: I José Nogueira Gualberto; G Araújo Medeiros; M Volpon Santos; L da Silva Lopes; H Rubens Machado; L Sbragia Journal: Childs Nerv Syst Date: 2022-07-30 Impact factor: 1.532
Authors: Richard H Finnell; Carlo Donato Caiaffa; Sung-Eun Kim; Yunping Lei; John Steele; Xuanye Cao; Gabriel Tukeman; Ying Linda Lin; Robert M Cabrera; Bogdan J Wlodarczyk Journal: Front Genet Date: 2021-05-10 Impact factor: 4.599