C57BL/6J-Csf1r^em1Peng/J

Stock number: 040606
Product name: Csf1r^I792T
Research areas: Cell Biology Research, Developmental Biology Research, Immunology, Inflammation and Autoimmunity Research, Neurobiology Research

Description

Csf1r^I792T mice have the I792T mutation in exon 18 of the Csf1r corresponding to the human mutation I794T. These mice may be useful for studying adult-onset leukoencephalopathy.

Of note the donating investigator also made Csf1r^E631K available as Stock No. 040607.

Detailed description

The colony stimulating factor 1 receptor (Csf1r) gene codes for a growth factor and tyrosine kinase receptor primarily involved in the development and differentiation of myeloid cells, particularly macrophages, microglia, and osteoclasts. Mutations in this gene have been associated with adult-onset leukoencephalopathy, which is a neurodegenerative disorder that leads to progressive behavioral and cognitive dysfunction, as well as motor impairment.

These Csf1r^I792T knock-in (KI) mice harbor the I792T mutation in exon 18, corresponding to the most common human mutation I794T associated with adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP).

Heterozygous mice are viable and fertile but display a progressive decline in motor functions by ~6 months of age based on longitudinal rotarod, balance beam and hindlimb clasping testing. By 12 months of age, these mice showed impaired recognition memory. Heterozygous mice also demonstrated significant microglial reductions and brain calcifications, which phenocopy human ALSP patients. Homozygous mice are perinatal lethal. These Csf1r^I792T KI mice may be useful for studying CSF1R-associated leukoencephalopathy.

Of note the donating investigator also made Csf1r^E631K available as Stock No. 040607.

Development

The Csf1r^I792T allele was generated using CRISPR/Cas9 endonuclease-mediated genome editing. A single guide RNA (5'-CAGTCCAAAGTCCCCAATCTTGG-3') was used to introduce the I792T mutation (p.Ile792Thr, c.T2375C, ATT>ACT) in exon 18 of the colony stimulating factor 1 receptor (Csf1r) gene on chromosome 18. Csf1r transcript Csf1r-201 (ENSMUST00000025523.13) was used as reference for the exon number and the guide sequences. The sgRNA, donor DNA carrying the I792T mutation flanked by ~60 bp homology arms, and Cas9 nuclease were introduced into the cytoplasm of zygotes derived from C57BL/6J (Stock No. 000664) mice with well recognized pronuclei. Correctly targeted pups were identified by PCR and sequencing. The resulting Csf1r^I792T mice were crossed to C57BL/6J mice for multiple generations by the donating laboratory to reduce off-target events. Upon arrival at The Jackson Laboratory, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes.

Allele

Symbol: Csf1r^em1Peng
Name: endonuclease-mediated mutation 1, Bo Peng
MGI accession ID: MGI:8204789
Generation method: Endonuclease-mediated
Attributes: Not Applicable
Synonyms: Csf1r^I792T
Marker symbol: Csf1r
Marker name: colony stimulating factor 1 receptor
Marker synonyms: BANDDOS; CD115; c-fms; CSF-1R; CSF-1-R; Csfmr; CSFR; Fim2; Fim-2; Fms; GPSC; HDLS; HDLS1; M-CSFR; M-CSF-R; mrfms
Chromosome: 18
Strain of origin: C57BL/6J
Molecular note: Using CRISPR/Cas9 endonuclease-mediated genome editing, a single guide RNA (5'-CAGTCCAAAGTCCCCAATCTTGG-3') was used to introduce the I792T mutation (p.Ile792Thr, c.T2375C, ATT>ACT) in exon 18 of the colony stimulating factor 1 receptor (Csf1r) gene.