All Phenotypes Cxcr4<tm1Yzo> MGI Mouse

lethality throughout fetal growth and development, incomplete penetrance ( J:69255 )

• homozygous mutant offspring were rarely born alive; those born alive died within a few hours after birth

• approximately 50% of homozygous mutant embryos died by E17.5

perinatal lethality, complete penetrance ( J:167314 )

• any embryos born alive died within a few hours after birth

decreased primordial germ cell number ( J:84597 )

• at E11.5, mutant embryos also displayed a striking decrease in the overall number of PGCs found in the genital ridge and the mesentery, suggesting a germ cell survival defect

• by E12.5, the number of PGCs in the genital ridge in both mutant and wild-type embryos increased by roughly the same amount, suggesting that germ cell survival and/or proliferation is not affected once PGCs reach the genital ridge

abnormal primordial germ cell migration ( J:84597 )

• homozygous mutant embryos displayed normal migration of primordial germ cells (PGCs) from the posterior primitive streak (E7.5) into the hindgut endoderm

• between E10.5-E11.5, PGCs displayed a significant delay in migration towards the genital ridge: compared with wild-type controls, mutant embryos showed a progressive reduction of PGCs colonizing the genital ridge, with more germ cells found along the mesentery and the hindgut

nervous system phenotype ( J:81783 )

N	• the developing neocortex and the developing pyramidal cell layer in Ammon's horn of the hippocampus appeared morphologically normal through E18.5

abnormal dentate gyrus morphology ( J:79852 , J:81783 )

• analysis of the migratory behavior of cells from the neuroepithelium to the dentate anlage revealed a defect in dentate granule cell migration; in E18.5 homozygotes, many dentate granule neurons appeared disorganized or were ectopically located outside the dentate gyrus, near the ventricular zone, above the fimbria and in the dentate migratory stream (J:79852)

• at E18.5, the hippocampal dentate gyrus (DG) of mutant mice appeared significantly smaller and morphologically immature (J:81783)

• gene expression markers for DG granule neurons and bromodeoxyuridine labeling of dividing cells indicated a deficit in the stream of postmitotic cells and secondary dentate progenitor cells that migrate toward and form the DG; in homozygotes, the number of dividing cells in the migratory stream and in the DG itself was reduced, and neurons appeared to differentiate prematurely (J:81783)

abnormal cerebral cortex morphology ( J:81783 )

• the mutant cerebral cortex was slightly smaller compared with wild-type; however, no obvious abnormalities were observed in cortical layer formation at E18.5

abnormal cerebellum morphology ( J:69255 )

• mutant cerebella diplayed normal patterning of neuronal layers in the caudal part close to the rhombic lip; however, the laminar structure of the cerebellum appeared abnormal

abnormal cerebellum external granule cell layer morphology ( J:69255 )

• mutant embryos displayed abnormal migration of cerebellar EGL cells: clusters of granule cells were located in ectopic sites, beneath the Purkinje cell layer or interspersed with Purkinje cells; in contrast to the granule cells, the Purkinje cells were situated correctly in mutant embryos

• the descending migration of EGL granule cells to form the internal granule layer (IGL), a postmitotic event that normally occurs postnatally, was observed prematurely (E17.5), and involved cells that continued to proliferate

• nonetheless, Bergmann cells were correctly localized with their fibers organized in a normal configuration and orientation; some mutant embryos showed an increase in the number of neuronal cells along the Bergmann glial fibers

abnormal leukopoiesis ( J:69255 )

• homozygous mutant mice displayed impaired B-cell lymphopoiesis

• in contrast, T-cell lymphopoiesis remained unaffected: both thymocyte maturation and subsequent emigration to lymphoid organs appeared normal

abnormal lymphopoiesis ( J:69255 )

• no cells expressing B220 or CD43 were detected in the mutant fetal liver or bone marrow, indicating that B-cell lymphopoiesis was arrested before the pro-B-cell stage

• mutant fetal liver cells failed to migrate towards ligand in an in vitro transwell chemotaxis assay

• in vitro clonal assays indicated that no substantial pro-B-cell clones were generated from cells of homozygous mutant mice upon cultivation of mutant fetal liver cells with the S17 stromal cell line

abnormal B cell differentiation ( J:167314 )

• B cell precursors are released into the peripheral blood and reduced in the spleen unlike in wild-type mice

impaired myelopoiesis ( J:69255 )

• homozygous mutant mice displayed normal myeloid developent in the fetal liver: fetal liver of cells of the myeloid lineage, including macrophages (CD11b+), granulocytes, monocytes (Gr1+, CD11b+) and megakaryocytes (CD61+), developed normally; however, the cellularity of these cell types was severely decreased in the bone marrow of mutant mice

abnormal B cell physiology ( J:167314 )

• pro-B cells fail to exhibit a chemotactic response towards CXCL12 compared with wild-type cells

• B cells exhibit only basal VCAM-1-binding activity in response to CXCL12 stimulation compared with similarly treated wild-type mice

abnormal interventricular septum morphology ( J:69255 )

• at E17.5, >70% of moribund mutant embryos exhibited dysplasia of the ventricular septum

decreased fetal size ( J:69255 )

• at E13.5, homozygous mutant embryos appeared macroscopically normal; however, at E17.5, viable mutant embryos displayed a reduced body size, with a mass averaging only 74% of wild-type embryos

hydrops fetalis ( J:69255 )

• at E17.5, >70% of moribund mutant embryos exhibited generalized edema