BACKGROUND AND PURPOSE: Spontaneous animal mutants affected by abnormal formation of myelin in the central nervous system (CNS) are useful in studies on myelinogenesis and remyelination leading to better understanding of cellular and molecular interactions involved in myelin repair. A novel rat mutant, Bouncer Long Evans (LE-bo) is severely dysmyelinated, but with exceptional longevity, and its clinical and pathologic phenotype are described. METHODS: Clinical observations, genetic studies, and determination of longevity were performed in a colony of rats, including carriers of LE-bo phenotype producing the mutant animals. Comprehensive histologic studies were performed on all perfusion-fixed tissues, and ultrastructural examination of the optic nerve and thoracic part of the spinal cord also was done in rats 1 to 14 weeks old. RESULTS: The LE-bo phenotype is characterized by whole body tremor, progressively severe ataxia, and severe seizure activity. The LE-bo phenotype is transferred as an autosomal recessive trait and is stable. The LE-bo rat can survive in good health beyond 45 weeks. Neuropathologic changes include severe global dysmyelination, with thin uncompacted myelin sheaths in young rats forming no major dense line, whereas the myelin sheaths of the peripheral nervous system appear normal. Oligodendrocytes degenerate with apparently progressing accumulation of membranous material in the perikaryon. Large numbers of immature glial cells were detected in the CNS of LE-bo rats at 4 to 14 weeks. CONCLUSION: The LE-bo rat is severely dysmyelinated due to inability of its oligodendrocytes to form myelin sheaths. Similarities of the LE-bo rat and Long Evans Shaker (les) rat neuropathologic features, such as severe dysmyelination, lack of major dense line in uncompacted myelin sheaths, apparent proliferation of oligodendroglial cells, and considerable longevity, are striking and suggest that a LE-bo mutation may functionally affect the myelin basic protein gene.
BACKGROUND AND PURPOSE: Spontaneous animal mutants affected by abnormal formation of myelin in the central nervous system (CNS) are useful in studies on myelinogenesis and remyelination leading to better understanding of cellular and molecular interactions involved in myelin repair. A novel rat mutant, Bouncer Long Evans (LE-bo) is severely dysmyelinated, but with exceptional longevity, and its clinical and pathologic phenotype are described. METHODS: Clinical observations, genetic studies, and determination of longevity were performed in a colony of rats, including carriers of LE-bo phenotype producing the mutant animals. Comprehensive histologic studies were performed on all perfusion-fixed tissues, and ultrastructural examination of the optic nerve and thoracic part of the spinal cord also was done in rats 1 to 14 weeks old. RESULTS: The LE-bo phenotype is characterized by whole body tremor, progressively severe ataxia, and severe seizure activity. The LE-bo phenotype is transferred as an autosomal recessive trait and is stable. The LE-bo rat can survive in good health beyond 45 weeks. Neuropathologic changes include severe global dysmyelination, with thin uncompacted myelin sheaths in young rats forming no major dense line, whereas the myelin sheaths of the peripheral nervous system appear normal. Oligodendrocytes degenerate with apparently progressing accumulation of membranous material in the perikaryon. Large numbers of immature glial cells were detected in the CNS of LE-bo rats at 4 to 14 weeks. CONCLUSION: The LE-bo rat is severely dysmyelinated due to inability of its oligodendrocytes to form myelin sheaths. Similarities of the LE-bo rat and Long Evans Shaker (les) rat neuropathologic features, such as severe dysmyelination, lack of major dense line in uncompacted myelin sheaths, apparent proliferation of oligodendroglial cells, and considerable longevity, are striking and suggest that a LE-bo mutation may functionally affect the myelin basic protein gene.
Authors: Heather VanSeggelen; Joanne A Hammill; Anna Dvorkin-Gheva; Daniela G M Tantalo; Jacek M Kwiecien; Galina F Denisova; Brian Rabinovich; Yonghong Wan; Jonathan L Bramson Journal: Mol Ther Date: 2015-06-30 Impact factor: 11.454
Authors: Yong Fang Zhu; Jacek M Kwiecien; Wojciech Dabrowski; Robert Ungard; Kan Lun Zhu; Jan D Huizinga; James L Henry; Gurmit Singh Journal: Mol Pain Date: 2018-10-16 Impact factor: 3.395
Authors: Wojciech Dabrowski; Jacek M Kwiecien; Radoslaw Rola; Michal Klapec; Greg J Stanisz; Edyta Kotlinska-Hasiec; Wendy Oakden; Rafal Janik; Margaret Coote; Benicio N Frey; Waldemar A Turski Journal: PLoS One Date: 2015-11-12 Impact factor: 3.240
Authors: Christopher W Helsen; Joanne A Hammill; Vivian W C Lau; Kenneth A Mwawasi; Arya Afsahi; Ksenia Bezverbnaya; Lisa Newhook; Danielle L Hayes; Craig Aarts; Bojana Bojovic; Galina F Denisova; Jacek M Kwiecien; Ian Brain; Heather Derocher; Katy Milne; Brad H Nelson; Jonathan L Bramson Journal: Nat Commun Date: 2018-08-03 Impact factor: 14.919