C57BL/6J-Acer2^em1Mvw/MvwJ

Stock number: 026793
Research areas: Cardiovascular Research, Hematological Research, Immunology, Inflammation and Autoimmunity Research

Description

This targeted disruption is valuable for characterizing sphingosine and sphingosine-1-phosphate regulation and their role in cardiovascular disease, lymphocyte migration and inflammation. Alkaline ceramidase 2 is the one ceramidase that has been found essential for the generation of normal levels of sphingosine in the blood. Mice homozygous for this allele have decreased levels, but not ablation, of sphingosine and its product sphingosine-1-phosphate, as well as decreased levels of total ceramides, in whole blood, plasma, erythrocytes, and platelets.

Detailed description

Alkaline ceramidase 2 (ACER2) is the one ceramidase that has been found essential for the generation of normal levels of sphingosine in the blood. Mice homozygous for this allele have decreased levels, but not ablation, of sphingosine and its product sphingosine-1-phosphate, as well as decreased levels of total ceramides, in whole blood, plasma, erythrocytes, and platelets. Bone marrow transplantation from null homozygotes into wild type hosts or wild type homozygotes into null hosts showed that this regulation comes from bone marrow-derived cells. Although sphingosine-1-phosphate has been shown to be important cardiovascular development and lymphocyte migration out of lymphoid tissues into the circulation, these Acer2 null homozygotes were not found to have cardiovascular defects or lymphopenia by two months of age.

Development

The Acer2^em1Mvw allele was generated by injecting C57BL/6J zygotes with Cas9 mRNA and two TRU-sgRNA guides, GACGTTGCTGATCTGGAG and GTGGGAACGGGACTGAA, selected to flank exon2. Founder 17, found to have a 452 bp deletion that includes all of exon 2 and a large portion of the adjacent intron, was backcrossed once to C57BL/6J and sperm was cryopreserved from heterozygous males.

Allele

Symbol: Acer2^em1Mvw
Name: endonuclease-mediated mutation 1, Jackson
MGI accession ID: MGI:5883755
Generation method: Endonuclease-mediated
Attributes: Null/Knockout
Marker symbol: Acer2
Marker name: alkaline ceramidase 2
Chromosome: 4
Strain of origin: C57BL/6J
Molecular note: A 452bp deletion removed the entire exon 2 and a large portion of the adjacent intron and western blot analysis failed to detect ACER2 protein in homozygotes.