B6.129S2-Ctf1^tm1Msd/J

Stock number: 022355
Research areas: Diabetes and Obesity Research, Neurobiology Research

Description

In this strain, a neo cassette replaces exon 2 and the coding region of exon 3 of the cardiotrophin 1 (Ctf1) gene, abolishing gene expression. These mice may be useful for studying the role of cardiotrophin 1 in neurogenesis and metabolism.

Detailed description

In this ct-1-/- strain, a neo cassette replaces exon 2 and the coding region of exon 3 of the cardiotrophin 1 (Ctf1) gene, abolishing gene expression. CT-1, a member of the gp130 family of cytokines, is highly expressed in embryonic skeletal muscle and promotes the survival of developing motor neurons. Through its activation of phosphatidylinositol 3-kinase, CT-1 acts to regulate fat and glucose metabolism. CT-1 has also been implicated in bone formation and myocardial remodeling. Homozygous mice are viable and fertile. Ct-1-/- mice exhibit increased cell death of developing motoneurons in spinal cord and brainstem in mice between E14 and the first postnatal week. They also have few cortical astrocytes and show reduction in muscle strength. These mice also display decreased energy expenditure, mature-onset obesity, insulin resistance, and hypercholesterolemia.

Development

A targeting vector was designed to replace exon 2 and the complete coding region of exon 3 of the cardiotrophin 1 (Ctf1) gene with a neomycin resistance (neo) cassette in reverse orientation to the gene. The construct was electroporated into 129S2/SvPas-derived D3 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts and the resulting chimeric males were bred to C57BL/6J females. The donating investigator reports that these ct-1-/- mice were bred for at least 10 generations to C57BL/6J background (see SNP note below). Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation to establish the colony.

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, 3 of 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed C57BL/6J ; C57BL/6N genetic background.

Allele

Symbol: Ctf1^tm1Msd
Name: targeted mutation 1, Michael Sendtner
MGI accession ID: MGI:2675769
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Ctf1
Marker name: cardiotrophin 1
Chromosome: 7
Strain of origin: 129S2/SvPas
Molecular note: A neomycin selection cassette replaced a genomic fragment spanning exon 2 and the complete coding region of exon 3. In situ hybridization studies on homozygous embryos demonstrated that no detectable transcript is expressed from this allele.