B6(129S4)-Zpld1^sprl/Kjn

Stock number: 028920
Research areas: Cell Biology Research, Developmental Biology Research, Sensorineural Research

Description

The spiral 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 more severe phenotype than that of the Zpld1^cwh mutation and much more severe phenotype than a targeted deletion.

Detailed description

Approximately half of the mice homozygous for the spiral mutation exhibit hyperactive circling behavior, and all have abnormal vestibulo-ocular reflex, but normal vestibular sensory evoked potential, normal hearing by ABR assessment and histologically normal cochlea, otolithic and vestibular organs. 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 more severe in spiral homozygotes than in mice homozygous for the Zpld1^cwh mutation (Stock No. 006123), but Zpld1^cwh homozygotes all display circling and heterozygotes also have reduced vestibulo-ocular gain, which is not found in spiral heterozygotes. 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 sprl allele do display some circling behavior. (Vijayakumar et al., 2019.)

Development

The spiral mutation arose spontaneously in the B6.129S4-Ccl2^tm1Rol/J strain in approximately 2012 and was backcrossed to C57BL/6J via backcross-intercross for 2 generations to breed out the Ccl2^tm1Rol allele. After this the strain was maintained by sibling intercrossing and sperm was cryopreserved in 2018 from homozygous males at generation N2F7. When the underlying mutation was defined it was determined that it arose in C57BL/6J-derived sequence.

Allele

Symbol: Zpld1^sprl
Name: spiral
MGI accession ID: MGI:6356635
Generation method: Spontaneous
Attributes: Null/Knockout
Marker symbol: Zpld1
Marker name: zona pellucida like domain containing 1
Marker synonyms: 9430016A21Rik; RGD1308138
Chromosome: 16
Strain of origin: B6.129S4-Ccl2^tm1Rol/J
Molecular note: A single C-to-T point mutation in exon 10 changing a CAG codon to TAG introducing a stop codon in place of a glutamine at amino acid 322 (p.Q322*), which is just after the furin cleavage site and eliminates the C-terminal region of the protein including the transmembrane domain.