title: Neurological deficits in mice with profound biotinidase deficiency are associated with demylination and axonal degeneration.
abstract: Biotinidase deficiency is an autosomal recessively inherited disorder characterized by neurological and cutaneous abnormalities. We have developed a transgenic knock-out mouse with biotinidase deficiency to better understand aspects of pathophysiology and natural history of the disorder in humans. Neurological deficits observed in symptomatic mice with biotinidase deficiency are similar to those seen in symptomatic children with the disorder. Using a battery of functional neurological assessment tests, the symptomatic mice performed poorly compared to wild-type mice. Demyelination, axonal degeneration, ventriculomegaly, and corpus callosum compression were found in the brains of untreated, symptomatic enzyme-deficient mice. With biotin treatment, the symptomatic mice improved neurologically and the white matter abnormalities resolved. These functional and anatomical findings and their reversal with biotin therapy are similar to those observed in untreated, symptomatic and treated individuals with biotinidase deficiency. The mouse with biotinidase deficiency appears to be an appropriate animal model in which to study the neurological abnormalities and the effects of treatment of the disorder.
authors.affiliation: Department of Medical Genetics, Henry Ford Hospital, Detroit, MI 48202, USA.
authors.forename: Kirit
authors.initials: K
authors.lastname: Pindolia
authors.forename: Jieli
authors.initials: J
authors.lastname: Chen
authors.forename: Cisley
authors.initials: C
authors.lastname: Cardwell
authors.forename: Xu
authors.initials: X
authors.lastname: Cui
authors.forename: Michael
authors.initials: M
authors.lastname: Chopp
authors.forename: Barry
authors.initials: B
authors.lastname: Wolf
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001369:Axons / Q000473:pathology; D043523:Biotinidase / Q000235:genetics; D028921:Biotinidase Deficiency / Q000150:complications* / Q000235:genetics; D001835:Body Weight / Q000235:genetics; D003337:Corpus Callosum / Q000473:pathology; D003711:Demyelinating Diseases / Q000209:etiology* / Q000235:genetics; D004195:Disease Models, Animal; D006849:Hydrocephalus / Q000175:diagnosis / Q000209:etiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009046:Motor Neurons / Q000473:pathology; D009186:Myelin Sheath / Q000235:genetics / Q000473:pathology; D009410:Nerve Degeneration / Q000209:etiology* / Q000235:genetics; D009422:Nervous System Diseases / Q000209:etiology* / Q000235:genetics; D011597:Psychomotor Performance / Q000502:physiology; D012018:Reflex / Q000235:genetics
chemical_list: D043523:Biotinidase