Mice homozygous for the Pitx3ak mutation exhibit microphthalmia (small eyes) and aphakia (no lens) related to arrested lens development. The mesencephalic dopamine system is malformed and as a result homozygotes fail to develop dopaminergic neurons of the substantia nigra (Smidt et al., 2004). Homozygotes display sensorimotor deficits specific to the nigrostriatal pathway such as the challenge beam and pole test and the test for spontaneous exploratory activitiy in a cylinder. These deficits can be reversed by L-DOPA administration (Hwang et al., 2005). This mutant mouse strain may be useful in studies of Parkinson's disease.
The aphakia allele arose spontaneously in 1981 on the 129S1/Sv-p+ Tyr+ KitlSl-J/J strain. A female with a small right eye was mated to a male with small left eye (male 1). The mating produced greater than 50% bilaterally aphakic pups. As a result of poor breeding on the original129S1 background, male 1 was mated to a C57BLKS/J female. The one F1 aphakic female produced was used to build the colony. The colony was maintained by occasional crossing to C57BLKS/J (Varnum et al. 1968). This strain was cryopreserved in 1984 using homozygous males at generation N5F39 or N5F40 bred to C57BL/6J females. The strain was cryo-recovered in 2005.
|Gene Symbol and Name||Pitx3, paired-like homeodomain transcription factor 3|
|Strain of Origin||129S1/Sv-KitlSl-J|
|Molecular Note||This allele carries a 652 bp deletion in the promoter region of the gene, located 2.5 kb upstream of the transcription start site. The deletion cosegregated with the aphakia phenotype. In situ hybridization studies of homozygous mutant mice did not detect transcripts in the lens placode or at later developmental stages of the lens.|