Targeted disruption of Pax1 defines its null phenotype and proves haploinsufficiency.
The murine paired box-containing gene Pax1 is required for normal development of the vertebral column, the sternum, and the scapula. Previous studies have shown that three natural Pax1 mouse mutants, the undulated alleles, exhibit phenotypes of different severity in these skeletal elements. Nevertheless, these analyses have not clarified whether the semidominant Undulated short-tail (Uns) mutation, in which the complete Pax1 locus is deleted, represents a null allele. Moreover, the analyses of the classical undulated mutants did not allow a conclusion with respect to haploinsufficiency of Pax1. To address both questions we have created a Pax1 null allele in mice by gene targeting. Surprisingly, the phenotype of this defined mutation exhibits clear differences to that of Uns. This result strongly indicates the contribution of additional gene(s) to the Uns mutant phenotype. Furthermore, the phenotype of mice heterozygous for the null allele demonstrates that Pax1 is haploinsufficient in some though not all skeletal elements which express Pax1 during embryonic development.
Wilm
B
B
GSF-National Research Center for Environment and Health, Institute of Mammalian Genetics, 85764 Neuherberg, Germany.
Dahl
E
E
Peters
H
H
Balling
R
R
Imai
K
K
D000818:Animals; D001483:Base Sequence; D001842:Bone and Bones / Q000002:abnormalities; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics*; D017353:Gene Deletion; D006239:Haplotypes; D006579:Heterozygote; D006720:Homozygote; D051379:Mice; D018345:Mice, Knockout; D051761:Paired Box Transcription Factors; D010641:Phenotype; D014157:Transcription Factors / Q000235:genetics*
D017931:DNA Primers; D004268:DNA-Binding Proteins; D051761:Paired Box Transcription Factors; D014157:Transcription Factors; C070835:PAX1 transcription factor