Fine Genetic and Comparative Mapping of the Deafness Mutation Ames waltzer on Mouse Chromosome 10 (original) (raw)

head tossing, and hyperactivity. Females are often poor The Ames waltzer (av) mouse mutant is an autosomal mothers. av mice swim only with difficulty and circle recessive deafness mutation on mouse Chromosome afloat. av 2J mice are reportedly more severely affected 10. Previously, av had not been mapped relative to moand sink in the swim test (Cook and Lane, 1993). lecular markers. We have performed an intersubspe-Previously, the av locus had been localized with low cific backcross with Mus musculus castaneus and resolution to phenotypic markers in the central region mapped microsatellite markers in this cross. Toothof Chromosome 10. It mapped about 43 cM proximal pick PCR on previously frozen tissue samples from offto silver (si) (Schaible, 1961) and 21-31 cM distal to spring was used as an efficient strategy to screen a the dystonia mutation, now known as laminin, a 2 (Lalarge number of animals quickly. In 1258 progeny ma2 dy) (Russell and Southard, 1966). No closely linked tested we found three recombinants for each of the markers have been reported. flanking markers D10Mit199 and D10Mit64. In addi-Central mouse Chromosome 10 has homologies to tion, nine different genes (Ank3, Bcr, Gnaz, Tfam, Mif, several human chromosomes (10q21-q22, 22q11, Mmp11, Dcoh, Pyp, and Gstt2) were mapped and elimi-21q22, 19p13) (Taylor et al., 1996). Human recessive nated genetically as candidate genes for av. av had deafness loci have been mapped to both 10q21 and been discussed as a potential mouse model for the hu-21q22 (Wayne et al., 1996; Chaib et al., 1996; Veske et man deafness loci Usher syndrome type ID (USH1D) al., 1996; Bonne-Tamir et al., 1996). In this study we and DFNB12. Comparative mapping shows that av report the fine genetic mapping of the av locus to closely maps near an evolutionary break point and makes it linked markers. Fine genetic mapping will not only unlikely that those loci are human homologues of av. facilitate positional cloning, but will also help to deter-A human homologue of av is predicted to lie either mine which, if any, human recessive deafness locus on 22q11.2 or on 10q21. The orientation of conserved linkage groups between these two human chromo-may be a homologue of av. somal regions relative to mouse Chromosome 10 was determined. ᭧ 1998 Academic Press MATERIALS AND METHODS Intersubspecific backcross. An intersubspecific backcross with Offspring were scored phenotypically at age 5-6 weeks. Two mea-ditory function in av mice (Osako and Hilding, 1971, sures were used: First it was observed if the animal was actively the only published description of Ames waltzer). Inicircling. If so, it was scored affected (av/av). If it was not circling it tially, all hair cells are formed but after about the 10th was tested for pinna response: A loud noise was generated out of day after birth the fluid spaces in the organ of Corti vision of the animal and it was observed if the ear (pinna) or the fail to develop. Subsequently during maturation the whole animal moved in response to the noise. This was repeated several times. Animals that responded were scored as unaffected (av/ spiral ganglion cells degenerate with gradual loss of /), those that did not, as affected (av/av). Most but not all animals hair cells. The permeability of the stria vascularis apgave consistent results. Once animals were scored, lung, liver, and pears to be normal (Osako and Hilding, 1971). In addispleen were removed and frozen in liquid nitrogen and stored at tion to deafness, av mice show typical circling behavior, 080ЊC for subsequent DNA analyses. DNA preparation. Small-scale DNA preparation was performed from an aliquot (1/10