The circler with hearing (cwh) mutation in Zpld1 causes vestibular dysfunction that is limited to the sensory input for rotary head movements but not linear accelerations and does not cause any auditory dysfunction. This allele causes a less severe phenotype than that of the Zpld1sprl mutation and much more severe phenotype than a targeted deletion.Read More +
Mice homozygous for the circler with hearing mutation exhibit hyperactive circling behavior with abnormal vestibulo-ocular reflex, but normal vestibular sensory evoked potential, normal hearing by ABR assessment and histologically normal cochlea, otolithic and vestibular organs. Homozygotes can swim to stay at the water’s surface, but swim in circles. This phenotype is consistent with the fact that ZPLD1 is expressed by cells that synthesize the components of the cupula, the membrane overlying the crista ampullaris of the semicircular canal, which is important for sensing the rotation of the head. The abnormality in vestibulo-ocular reflex is less severe in circler with hearing homozygotes than in mice homozygous for the Zpld1sprl mutation (Stock No. 028920) but only approximately half of the Zpld1sprl homozygotes display the circling phenotype. A targeted deletion of Zpld1 (Stock No. 031591) does not cause circling behavior although approximately one quarter of compound heterozygotes with one null and one Zpld1sprl allele do display some circling behavior. Mice heterozygous for the circler with hearing mutation also have reduced vestibulo-ocular gain, but less severe than do homozygotes, and one in 37 displayed circling. (Vijayakumar et al., 2019.)
The circling with hearing mutation arose spontaneously in the B6.129P2-Nos2tm1Lau/J strain in approximately 1999 and was backcrossed to C57BL/6J via backcross-intercross for 5 generations during which the Nos2tm1Lau allele was bred out. This mutant sub-line was subsequently maintained by sibling intercrossing. When the underlying mutation was defined it was determined that it arose in C57BL/6J-derived sequence. Sperm was cryopreserved in 2011 from homozygous males at generation N5F9.
|Allele Name||circler with hearing|
|Allele Type||Spontaneous (Not Specified)|
|Gene Symbol and Name||Zpld1, zona pellucida like domain containing 1|
|Strain of Origin||B6.129P2-Nos2tm1Lau/J|
|Molecular Note||A single point mutation in exon 4, c.155A>T, changes an AAG codon to AUG changing a lysine to methionine at residue 52 (p.K52M), which is in the zona pelucida domain.|
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