Genetically modified mouse models to study Ackr3 expression in vivo and associated phenotypes

ModelGenetic BackgroundDescriptionReferences
Constitutive deletion
 Ackr3−/−C57Bl/6Mice carrying loxP-flanked Ackr3 exon 2 crossed with Deleter-Cre miceSierro et al. (2007), Sánchez-Alcañiz et al. (2011), Wang et al. (2011), Yu et al. (2011), Trousse et al. (2015)
Phenotype: Perinatal death of >95% Ackr3−/− mice.
Thickened semilunar valves. Normal development of B cells and granulocytes. Altered neuron migration during embryonic development.
 Ackr3−/−129 Sv/Ev x C57Bl/6Knock-in of LacZ reporter in Ackr3 exon 2 (IRES-LacZ/PGK- Neo cassette)Gerrits et al. (2008)
Phenotype: Perinatal death of 70% Ackr3/− mice.
Nonviable mice: Myocardial degeneration, fibrosis, and cardiac hyperplasia. No defects in semilunar valves.
Surviving mice: Cardiac hyperplasia in 25%. Normal lifespan, no hematopoietic or hematologic defects, no reproductive defects.
Conditional (tissue- or cell type–specific) deletion
 Tie2-Cre; Ackr3flox/−C57Bl/6Endothelium-specific deletion.Sierro et al. (2007), Yu et al. (2011)
Phenotype: Mice survive to adulthood and are fertile.
Cardiac hypertrophy, thickened ventricular walls, and thickened semilunar valves in 40% of the mice.
 Dlx5/6-Cre; Ackr3flox/floxC57Bl/6GABAergic neuron-specific deletion.Sánchez-Alcañiz et al. (2011)
Phenotype: Mice survive to adulthood. Altered migration of neurons during embryonic development (E16.5).
 DlxI12b-Cre; Ackr3flox/−C57Bl/6 CD1GABAergic neuron-specific deletion.Wang et al. (2011)
Phenotype: Neuron positioning defects similar to those of constitutive Ackr3 /− mice.
 Emx1-Cre; Ackr3flox/−Not givenGlutamatergic neuron-specific deletion.Wang et al. (2011)
Phenotype: No effect on the position of cortical projection neurons.
 Tbr2-Cre; Ackr3flox/floxNot givenGlutamatergic neuronal progenitor-specific deletion. Phenotype: Altered migration of neurons in adulthood.Abe et al. (2018)
 Dbx1-Cre; Ackr3flox/floxC57Bl/6Cajal-Retzius neuron progenitor-specific deletion.Trousse et al. (2015)
Phenotype: Defects in the positioning of a subpopulation of Dbx1-expressing neurons during embryonic development (E14.5).
Conditional-inducible (cell type-specific inducible) deletion
 Scl-CreERT; Ackr3floxC57Bl/6Tamoxifen-inducible deletion of Ackr3 from Scl-expressing cells (HSC, myeloid lineage, endothelium and regions in the central nervous system) in adult mice.Stacer et al. (2016)
Findings: ∼35% increase in CXCL12 plasma levels. No other apparent phenotype described.
Reporter gene
 Ackr3+/EGFPC57Bl/6Replacement of Ackr3 exon 2 by EGFP. No phenotype is described.Cruz-Orengo et al. (2011)
 Ackr3-EGFPCD1BAC insertion of the Ackr3 promoter fused to an EGFP coding region. Endogenous Ackr3 locus remains intact. No secondary effects.The Gene Expression Nervous System Atlas (GENSAT)
Gong et al. (2003)