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Localization of the Mouse nob (no b-wave) Gene to the Centromeric Region of the X Chromosome

From the Departments of ¹ Biochemistry and Molecular Biology, ⁴ Psychological and Brain Sciences, and ⁵ Ophthalmology and Visual Sciences, University of Louisville, Kentucky; ² Research Service, Hines VA Hospital, Hines, Illinois; Departments of ³ Neurology and ⁶ Ophthalmology, Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois.

PURPOSE. To determine the position on the X chromosome of the gene responsible for a spontaneous mouse mutation, nob (no b-wave), which matches the phenotype of complete X-linked congenital stationary night blindness (CSNB) type 1 in human.

METHODS. Inter- and intraspecific pedigrees were generated, and the phenotype of each mouse was scored on the basis of either the presence or the absence of an electroretinographic b-wave. DNA was isolated from a tail biopsy from each mouse and was used to determine the genotype at various polymorphic markers on the X chromosome. LOD scores (Z) between the nob phenotype and each marker were calculated to determine the most probable location of the nob gene.

RESULTS. A total of 174 informative offspring were analyzed. The nob gene is tightly linked to DXMit103 with a maximum LOD score of 25.9 at a recombination fraction of zero. This marker is located at 4.2 cM on the X chromosome of the mouse map. Haplotype analyses of several recombinant chromosomes in the region indicates that the nob gene maps between DXMit54 (3.8 cM) and Ube1x (5.7 cM).

CONCLUSIONS. The genetic position of the mouse nob gene overlaps the homologous region in human that contains the locus for CSNB1 and excludes the region of CSNB2. Further studies are planned to identify the mouse nob gene and to evaluate it as a candidate for CSNB1.

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