C57BL/6J-Clp1^em2Slac/J

Stock number: 036710
Product name: Clp1 null, c.414-429Δ, c.414-429del
Research areas: Cell Biology Research, Neurobiology Research

Description

Clp1 null (c.414-429Δ, c.414-429del) mice carry a CRISPR/Cas9-generated knock-out of the mouse Clp1 (CLP1, cleavage and polyadenylation factor I subunit) gene. Heterozygotes show no overt phenotype. Homozygotes cannot be recovered at embryonic day 7.5 (E7.5). This strain is useful in studies of pontocerebellar hypoplasia type 10 (PCH10), a pediatric neurodegenerative disease.

Detailed description

CLP1 (CLP1, cleavage and polyadenylation factor I subunit) is associated with the tRNA splicing endonuclease complex and the cleavage and polyadenylation machinery. Mutation of the human RNA kinase causes pontocerebellar hypoplasia type 10 (PCH10), a pediatric neurodegenerative disease.

Clp1 null (c.414-429Δ, c.414-429del) mice carry a CRISPR/Cas9-generated knock-out of the mouse Clp1 gene. Heterozygotes show no overt phenotype. Homozygotes cannot be recovered at embryonic day 7.5 (E7.5).

Mice heterozygous for both this Clp1 null mutation and Clp1^R140H (Stock No. 036709) develop severe motor defects. This phenotype better approximates the condition of patients with PCH10 than the phenotype of mice homozygous for the Clp1^R140H mutation does. Onset of the motor defects in the compound mutant mice is between 2-3 weeks of age.

Clp1^R140H/Clp1 null compound mutant mice and Clp1^R140H homozygotes both develop motor impairments and progressive loss of lower motor neurons in the spinal cord and in the deep cerebellar nuclei (DCN). Mutants also have altered tRNA metabolism, however it is not clear whether these alterations contribute to pathogenesis.

Development

A 16 bp deletion mutation was introduced to the first coding exon (exon 2) of the mouse Clp1 gene via CRISPR/Cas9 methodologies (gRNA c.403-422; NM_133840.2). The mutation was created in C57BL/6J embryos. Resultant mice were backcrossed to C57BL/6J for at least 2 generations by the donating laboratory.

Allele

Symbol: Clp1^em2Slac
Name: endonuclease-mediated mutation 2, Susan L Ackerman
MGI accession ID: MGI:6759437
Generation method: Endonuclease-mediated
Attributes: Null/Knockout
Marker symbol: Clp1
Marker name: CLP1, cleavage and polyadenylation factor I subunit
Marker synonyms: hClp1; Heab; RGD1307679
Chromosome: 2
Strain of origin: C57BL/6J
Molecular note: CRISPR/cas9 genome editing is used to introduce a 16 bp deletion (gRNA c.403-422; NM_133840.2; deletion is c.414-429) mutation to the first coding exon (exon 2), creating a frameshift after codon 139 (of 425) and shortly followed by a termination codon.