Pm. Nolan et al., HETEROZYGOSITY MAPPING OF PARTIALLY CONGENIC LINES - MAPPING OF A SEMIDOMINANT NEUROLOGICAL MUTATION, WHEELS (WHL), ON MOUSE CHROMOSOME-4, Genetics, 140(1), 1995, pp. 245-254
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 respon
ses to light. In this report, we genetically and phenotypically charac
terized the circling/waltzing component of the abnormal behavior. We m
apped the locus controlling this trait by heterozygosity mapping of pa
rtially 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 loc
us, named Wheels (Whl), resides in the subcentromeric portion of mouse
chromosome 4. The statistical evaluation of data obtained by heterozy
gosity mapping validates this efficient mapping approach. Further char
acterization of the Whl mutation demonstrated that Whl/Whl homozygotes
die during embryonic life and that the penetrance of circling behavio
r depends on genetic background. Morphological analysis of the inner e
ars of Whl/+ mice revealed a variable number of abnormalities in the s
ensory and nonsensory portions of their semicircular canals. Abnormali
ties ranged from slight atrophy of one or more cristae to complete abs
ence of the lateral crista and canal. The molecular characterization o
f the gene disrupted in the Whl mutation will provide insight into dev
elopmental mechanisms involved in inner ear formation.