Genetic mapping of agenesis of the third molars in mice.

EL/Sea mice are characterized by 100% incidence of agenesis of the third molars (M3). In a previous study, chromosomal mapping of the ninth generation EL/Sea congenic strains revealed a major locus for agenesis of M3, designated am3, in the 125-137 Mbp region of chromosome 3. In the present study, to determine the precise location of the am3 locus, we produced further generations of the EL/Sea congenic strains for am3 in which the restricted interval on chromosome 3 of EL/Sea was replaced by a MSM/Msf-derived homolog. The eleventh generation congenic mice that were either heterozygous or homozygous for the MSM/Msf-derived interval exhibited a significant decrease in the incidence of M3 agenesis (p < 0.00001). Results confined the am3 locus to an interval of 1 Mbp on chromosome 3, demonstrating that Lef1, one of the essential transcription factors for early tooth development, is the strongest candidate for am3.