C57BL/6J-Clp1^em1Slac/J

Stock number: 036709
Product name: Clp1^R140H, c.419G>A
Research areas: Cell Biology Research, Neurobiology Research

Description

Clp1^R140H (c.419G>A) mice carry a CRISPR/Cas9-generated arginine to histidine missense mutation (R140H) in the mouse Clp1 (CLP1, cleavage and polyadenylation factor I subunit) gene. This mutation is homologous to one found in pontocerebellar hypoplasia type 10 (PCH10) patients. Homozygotes develop motor impairments and progressive loss of lower motor neurons in the spinal cord and in the deep cerebellar nuclei (DCN).

Detailed description

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

Clp1^R140H (c.419G>A) mice carry a CRISPR/Cas9-generated arginine to histidine missense mutation (R140H) in the mouse Clp1 gene that is homologous to one found in PCH10 patients. Protein expression levels have not been examined (September, 2021).

Clp1^R140H heterozygotes are unremarkable. Mice homozygous for the point mutation are born at predicted Mendelian ratios and have no overt behavioral or morphological phenotypes at postnatal day 14, but they develop progressive tremor and altered gait beginning at 3‐4 months of age. Homozygous females (and subsequently males) begin to weigh less than wildtype controls around one month of age. They appear to live a normal lifespan.

Mice heterozygous for both this Clp1^R140H allele and a Clp1 null allele (Stock No. 036710) 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.

Development

A c.419G>A mutation was introduced to the first coding exon (exon 2) of the mouse Clp1 gene via CRISPR/Cas9 methodologies (gRNA c.403-422; donor oligo c357-486 with c.419G>A and c.426C>A; 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^em1Slac
Name: endonuclease-mediated mutation 1, Susan L Ackerman
MGI accession ID: MGI:6759435
Generation method: Endonuclease-mediated
Attributes: Humanized sequence
Synonyms: Clp1^R140H
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 G to A mutation (gRNA c.403-422; donor oligo c357-486 with c.419G to A and c.426C to A; NM_133840.2) at position 419 resulting in an arginine to histidine missense mutation (R140H) in the first coding exon (exon 2). The mutation homologous to one found in pontocerebellar hypoplasia type 10 (PCH10) patients.