title: A novel phenotypic marker for ATM-deficient 129S6/SvEvTac-ATMtm1Awb/J mice.
abstract: Ataxia-telangiectasia (A-T) is a human autosomal recessive disorder characterized by neuronal degeneration as well as many other physiological and somatic defects. ATM (A-T, mutated), the gene mutated in A-T, encodes a 370 kDa protein kinase. ATM knockout mouse models (ATM(-/-)) show growth retardation, infertility, neurological dysfunction, defects in T-lymphocytes, and extreme sensitivity to ionizing radiation. We have recently established multiple ATM(+/-) breeding pairs and discovered that all ATM(-/-) offspring exhibit a nonpigmented section of tail, usually at or near the tip. To our knowledge, this is the first time that a phenotype of nonpigmented tail has been reported in ATM(-/-) knockout mice. We believe that the sections of nonpigmented tail of 129S6/SvEvTac-ATM(tm1Awb)/J mice provide a novel phenotypic marker for research using this ATM knockout mouse model. Results from histochemistry and immunoblotting analysis further demonstrate that while melanocyte precursors or melanoblasts are present in the nonpigmented tail tissue of ATM(-/-) mice, they fail to differentiate fully into mature melanocytes. The potential connection between this phenotype and other clinical symptoms caused by ATM deficiency, such as progressive neuronal degeneration, is discussed in this article.
authors.affiliation: Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, South Dakota 57069, USA.
authors.forename: Jody C
authors.initials: JC
authors.lastname: Hibma
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Neufeld
authors.forename: Marie-Jo
authors.initials: MJ
authors.lastname: Halaby
authors.forename: Da-Qing
authors.initials: DQ
authors.lastname: Yang
mesh_terms: D000818:Animals; D001260:Ataxia Telangiectasia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D064007:Ataxia Telangiectasia Mutated Proteins; D015415:Biomarkers / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D005838:Genotype; D017496:Hypopigmentation / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D019746:Intramolecular Oxidoreductases / Q000378:metabolism; D008543:Melanins / Q000172:deficiency / Q000378:metabolism*; D008544:Melanocytes / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D014442:Monophenol Monooxygenase / Q000378:metabolism; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013623:Tail / Q000378:metabolism* / Q000473:pathology; D025521:Tumor Suppressor Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D008543:Melanins; D025521:Tumor Suppressor Proteins; D014442:Monophenol Monooxygenase; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; C576325:Atm protein, mouse; D017346:Protein Serine-Threonine Kinases; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase