title: Heterozygosity mapping of partially congenic lines: mapping of a semidominant neurological mutation, Wheels (Whl), on mouse chromosome 4.
abstract: We identified a semidominant, chemically induced, mouse mutation with a complex array of abnormal behaviors including bidirectional circling and hyperactivity, abnormal circadian rhythmicity and abnormal responses to light. In this report, we genetically and phenotypically characterized the circling/waltzing component of the abnormal behavior. We mapped the locus controlling this trait by heterozygosity mapping of partially congenic lines carrying the mutagenized chromosome outcrossed to different inbred strains for three generations. Analysis of 68 PCR-based markers in 13 affected individuals indicated that the mutant locus, named Wheels (Whl), resides in the subcentromeric portion of mouse chromosome 4. The statistical evaluation of data obtained by heterozygosity mapping validates this efficient mapping approach. Further characterization of the Whl mutation demonstrated that Whl/Whl homozygotes die during embryonic life and that the penetrance of circling behavior depends on genetic background. Morphological analysis of the inner ears of Whl/+ mice revealed a variable number of abnormalities in the sensory and nonsensory portions of their semicircular canals. Abnormalities ranged from slight atrophy of one or more cristae to complete absence of the lateral crista and canal. The molecular characterization of the gene disrupted in the Whl mutation will provide insight into developmental mechanisms involved in inner ear formation.
authors.affiliation: Department of Psychiatry, University of Pennsylvania, Philadelphia 19104, USA.
authors.forename: P M
authors.initials: PM
authors.lastname: Nolan
authors.forename: P J
authors.initials: PJ
authors.lastname: Sollars
authors.forename: B A
authors.initials: BA
authors.lastname: Bohne
authors.forename: W J
authors.initials: WJ
authors.lastname: Ewens
authors.forename: G E
authors.initials: GE
authors.lastname: Pickard
authors.forename: M
authors.initials: M
authors.lastname: Bućan
mesh_terms: D000818:Animals; D002874:Chromosome Mapping; D002940:Circadian Rhythm / Q000235:genetics; D005799:Genes, Dominant; D005819:Genetic Markers; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008818:Mice, Neurologic Mutants / Q000235:genetics*; D009043:Motor Activity / Q000235:genetics; D016133:Polymerase Chain Reaction; D012665:Semicircular Canals / Q000002:abnormalities*
chemical_list: D005819:Genetic Markers