C57BL/6-Prickle1^m2Ingm/J

Stock number: 027725
Product name: Prickle1Cys251X
Research areas: Developmental Biology Research, Neurobiology Research

Description

Prickle1^Cys251X mutant mice possess an ENU-induced point mutation in the Prickle1 gene that results in a decreased seizure threshold. They may be useful for studies of epilepsy and seizures.

Detailed description

The Prickle1 gene encodes a nuclear receptor that is essential in planar cell polarity signaling pathway that may be a negative regulator of the Wnt/beta-catenin signaling pathway. Mutations in the human PRICKLE1 gene are associated with progressive myoclonus epilepsy.

These Prickle1^Cys251X chemically-induced (ENU) mutant mice carry a nonsense mutation in exon 6 of the Prickle1 gene, which results in a premature stop codon at the 251 amino acid from N-terminal, in the third LIM domain. The truncated protein lacks the 3rd LIM domain as well as the nuclear localization sequence.

Mice heterozygous for the mutation are viable, fertile and exhibit lower seizure threshold compare to wildtype controls (as assessed by maximal electroshock seizure threshold). Homozygotes have a perinatal lethal phenotype.

Development

Male C57BL/6J mice were treated with multidose N-ethyl-N-nitrosourea (ENU). A founder animal identified from the mutagenesis screen and carrying the Cys251X point mutation was backcrossed to C57BL/6 using a rapid congenic protocol. The mutation introduces a premature stop codon at the 251 amino acid from N-terminal, in the third LIM domain. Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes (Stock No. 000664).

Allele

Symbol: Prickle1^m2Ingm
Name: mutation 2, Ingenium Pharmaceuticals
MGI accession ID: MGI:4941929
Generation method: Chemically induced (ENU)
Marker symbol: Prickle1
Marker name: prickle planar cell polarity protein 1
Chromosome: 15
Strain of origin: C57BL/6J
Molecular note: ENU mutagenesis induced the amino acid substitution of a stop codon for cysteine at position 251 (C251X).