(A) Schematic representation of Cxcl12 genomic locus, targeting vector and recombined Cxcl12 locus (Cxcl12Gagtm). Exons 1-4 are represented by darked boxes. Mutations incorporating residue substitutions (2nd exon) and stop codon (4th exon) are indicated by vertical arrows and stars. The LoxP-FRT-Neo cassette is inserted in an opposite orientation regarding to the target gene in intron 3-4. Long (LA) and short (SA) homology arm positions and length are indicated. (B) Hematoxylin and eosin staining of bone marrow (left panels), cerebellum (middle panels) and skeletal muscle (right panels) tissue sections from Cxcl12Gagtm/Gagtm (MUT) and wild-type littermate (WT) animals. Arrows show megakaryocytes; 1 display white substance; 2, granular layer; 3, molecular layer. (C) Real-time PCR analysis of Cxcl12. Relative RNA expression levels of Cxcl12 isoforms normalized to HPRT in cerebellum, bone marrow and skeletal muscle tissues. Cxcl12α, Cxcl12β and Cxcl12γ ARN levels on MUT animals are expressed relative to the WT animals level, arbitrary set to 1 (n=12 per group). (D). CXCL12 levels in blood were measured by ELISA in MUT and WT animals. (E) Cell populations in peripheral blood collected from MUT and WT animals. Results are mean±SEM. **p<0.01, ***p<0.001 versus WT.