title: Characterization and functional analysis of cellular immunity in mice with biotinidase deficiency.
abstract: Biotinidase deficiency is an autosomal recessively inherited metabolic disorder that can be easily and effectively treated with pharmacological doses of the vitamin, biotin. Untreated children with profound biotinidase deficiency may exhibit neurological, cutaneous and cellular immunological abnormalities, specifically candida infections. To better understand the immunological dysfunction in some symptomatic individuals with biotinidase deficiency, we studied various aspects of immunological function in a genetically engineered knock-out mouse with biotinidase deficiency. The mouse has no detectable biotinidase activity and develops neurological and cutaneous symptoms similar to those seen in symptomatic children with the disorder. Mice with profound biotinidase deficiency on a biotin-restricted diet had smaller thymuses and spleens than identical mice fed a biotin-replete diet or wildtype mice on either diet; however, the organ to body weight ratios were not significantly different. Thymus histology was normal. Splenocyte subpopulation study showed a significant increase in CD4 positive cells. In addition, in vitro lymphocyte proliferation assays consistently showed diminished proliferation in response to various immunological stimuli. Not all symptomatic individuals with profound biotinidase deficiency develop immunological dysfunction; however, our results do show significant alterations in cellular immunological function that may contribute and/or provide a mechanism(s) for the cellular immunity abnormalities in individuals with biotinidase deficiency.
authors.affiliation: Department of Medical Genetics, Henry Ford Hospital, Detroit, MI 48202, USA; Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI 48201, USA.
authors.forename: Kirit
authors.initials: K
authors.lastname: Pindolia
authors.affiliation: Division of Genetic and Metabolic Disorders, Children's Hospital of Michigan, Detroit, MI 48201, USA; Department of Human Genetics, Emory University School of Medicine, Decatur, GA 30033, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Medical Genetics, Henry Ford Hospital, Detroit, MI 48202, USA.
authors.forename: Cisley
authors.initials: C
authors.lastname: Cardwell
authors.affiliation: Department of Medical Genetics, Henry Ford Hospital, Detroit, MI 48202, USA; Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI 48201, USA. Electronic address: bwolf1@hfhs.org.
authors.forename: Barry
authors.initials: B
authors.lastname: Wolf
mesh_terms: D000818:Animals; D001710:Biotin / Q000008:administration & dosage* / Q000627:therapeutic use; D043523:Biotinidase / Q000235:genetics / Q000378:metabolism; D028921:Biotinidase Deficiency / Q000178:diet therapy* / Q000276:immunology* / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D007111:Immunity, Cellular / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013154:Spleen / Q000254:growth & development / Q000276:immunology; D013950:Thymus Gland / Q000254:growth & development / Q000276:immunology
chemical_list: D001710:Biotin; D043523:Biotinidase
keywords: Biotin; Biotinidase; Biotinidase deficiency; Biotinidase-deficient mouse; Cellular immunity; Multiple carboxylase deficiency