Phenotypes associated with this allele

• Allele Symbol: Cxcr4^tm1Tng
• Allele Name: targeted mutation 1, Takashi Nagasawa
• Allele ID: MGI:1934442
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Cxcr4^tm1Tng/Cxcr4^tm1Tng	B6.Cg-Cxcr4^tm1Tng	MGI:3045439
hm2	Cxcr4^tm1Tng/Cxcr4^tm1Tng	involves: 129P2/OlaHsd	MGI:3045435
cn3	Cxcr4^tm1Tng/Cxcr4^tm2Tng Tg(Tek-cre)12Flv/0	involves: 129P2/OlaHsd * C3H * C57BL/6	MGI:5502187
cn4	Cd19^tm1(cre)Cgn/Cd19^+ Cxcr4^tm1Tng/Cxcr4^tm2Tng	involves: 129P2/OlaHsd * C57BL/6	MGI:3639683

Genotype
MGI:3045439

hm1

• Allelic Composition: Cxcr4^tm1Tng/Cxcr4^tm1Tng
• Genetic Background: B6.Cg-Cxcr4^tm1Tng

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

hematopoietic system

abnormal T cell differentiation ( J:82996 )

• at E11.5, mutant embryos on a C57BL/6 background showed normal accumulation of T cell precursors in the outer mesenchymal layer of the thymus anlage during initial colonization

• fetal thymi contained relatively normal or slightly reduced numbers of CD3-CD4-CD8- triple-negative (TN) CD44+CD25- and TN CD44+CD25+ cells but substantially reduced numbers of TN CD44-CD25+, TN CD44-CD25-, and CD4+CD8+ double-positive (DP) cells from E13.5 onward

• enforced expression of Bcl2 failed to rescue impaired T cell development

decreased double-positive T cell number ( J:82996 )

• the numbers of CD4+CD8+ DP thymocytes were reduced 5-fold at E18.5

immune system

abnormal T cell differentiation ( J:82996 )

• at E11.5, mutant embryos on a C57BL/6 background showed normal accumulation of T cell precursors in the outer mesenchymal layer of the thymus anlage during initial colonization

• fetal thymi contained relatively normal or slightly reduced numbers of CD3-CD4-CD8- triple-negative (TN) CD44+CD25- and TN CD44+CD25+ cells but substantially reduced numbers of TN CD44-CD25+, TN CD44-CD25-, and CD4+CD8+ double-positive (DP) cells from E13.5 onward

• enforced expression of Bcl2 failed to rescue impaired T cell development

decreased double-positive T cell number ( J:82996 )

• the numbers of CD4+CD8+ DP thymocytes were reduced 5-fold at E18.5

reproductive system

abnormal primordial germ cell migration ( J:83291 )

• from E12.5 to E13.5, mutant embryos on a congenic C57BL/6 background showed a similar expansion of primordial germ cells (PGCs) in the gonads

• at E13.5 or E14.5, the numbers of PGCs in gonads from mutant embryos were significantly reduced, suggesting abnormal homing of PGCs into genital ridges

• in contrast, emigration of PGCs into the endoderm or mesentery of hindgut appeared unaffected

cellular

abnormal primordial germ cell migration ( J:83291 )

• from E12.5 to E13.5, mutant embryos on a congenic C57BL/6 background showed a similar expansion of primordial germ cells (PGCs) in the gonads

• at E13.5 or E14.5, the numbers of PGCs in gonads from mutant embryos were significantly reduced, suggesting abnormal homing of PGCs into genital ridges

• in contrast, emigration of PGCs into the endoderm or mesentery of hindgut appeared unaffected

Genotype
MGI:3045435

hm2

• Allelic Composition: Cxcr4^tm1Tng/Cxcr4^tm1Tng
• Genetic Background: involves: 129P2/OlaHsd

mortality/aging

neonatal lethality, complete penetrance ( J:69256 )

• the remaining neonates died within an hour after birth

perinatal lethality, incomplete penetrance ( J:69256 )

• homozygotes were present at the expected ratios until E15.5

• about 50% of embryos died at E18.5

integument

abnormal skin vasculature morphology ( J:195048 )

• mice exhibit a failure of nerve-vessel alignment in developing limb skin compared with wild-type mice

• however, vascular density is normal

cardiovascular system

cardiovascular system phenotype ( J:69256 )

N • at E18.5, most major blood vessels, including the superior mesenteric artery (SMA) and vein (SMV), appeared histologically normal

abnormal skin vasculature morphology ( J:195048 )

• mice exhibit a failure of nerve-vessel alignment in developing limb skin compared with wild-type mice

• however, vascular density is normal

abnormal angiogenesis ( J:69256 )

• at E11.5, mutant embryos displayed a normal highly-branched vascular network in the gastrointestinal tract

• at E13.5, mutant mesenteries contained abnormally smaller branches of superior mesenteric artery (SMA) or vein (SMV) relative to wild-type

• at E13.5, wild-type mesenteries contained the SMA, SMV and their paired branches (each branch contained the artery and the vein); in contrast, most of the mutant branches were single

• at E17.5, wild-type large mesenteric vessels were split into many branches and reached one side of the intestine; in mutant embryos large mesenteric vessels were almost absent, and there were fewer large vessels with aberrant branching

• similarly, the large vessels of the stomach arising from the mesenchymal vessels were absent at E15.5; in contrast, the small vascular network that surrounds the stomach remained unaffected

poor arterial differentiation ( J:195048 )

abnormal developmental vascular remodeling ( J:195048 )

• disorganized branching patterns in developing limb skin

abnormal vasculogenesis ( J:178190 )

• reduced connections between the superior mesenteric artery and the capillary plexus of the midgut loop at E15.5

abnormal vascular smooth muscle morphology ( J:195048 )

• reduced smooth muscle cell coverage of small diameter branched vessels

• however, coverage of large diameter veins is normal

abnormal heart morphology ( J:178190 )

thick mitral valve cusps ( J:178190 )

• sometimes fused as well

ventricular septal defect ( J:178190 )

• at E14.5

perimembraneous ventricular septal defect ( J:69256 )

• at E18.5, mutant embryos displayed defects of the membranous portion of the cardiac ventricular septum

abnormal heart right ventricle outflow tract morphology ( J:178190 )

• double outlet at E14.5

small intestine hemorrhage ( J:69256 )

• at E16.5, mutant embryos had multiple hemorrhages and/or congestion in the small intestine

digestive/alimentary system

digestive/alimentary phenotype ( J:69256 )

N • the stomachs and intestines of E18.5 mutant embryos were grossly normal

small intestine hemorrhage ( J:69256 )

• at E16.5, mutant embryos had multiple hemorrhages and/or congestion in the small intestine

embryo

embryo phenotype ( J:69256 )

N • homozygous null embryos showed normal formation of large and small vessels in the yolk sac (E12.5, E14.5), head region, (E11.5), and developing heart (E12.5-14.5)

N • vitellin and umbilical vessels appeared normal

hematopoietic system

abnormal B cell differentiation ( J:69256 )

• fetal livers displayed a severe reduction in the number of B-cell progenitors

failure of myelopoiesis ( J:69256 )

• developing hematopoietic cells found in wild-type bone marrow were absent in mutant bone marrow

immune system

abnormal B cell differentiation ( J:69256 )

• fetal livers displayed a severe reduction in the number of B-cell progenitors

failure of myelopoiesis ( J:69256 )

• developing hematopoietic cells found in wild-type bone marrow were absent in mutant bone marrow

muscle

abnormal vascular smooth muscle morphology ( J:195048 )

• reduced smooth muscle cell coverage of small diameter branched vessels

• however, coverage of large diameter veins is normal

nervous system

nervous system phenotype ( J:195048 )

N • mice exhibit normal innervation accompanied by migrating Schwann cells

Genotype
MGI:5502187

cn3

• Allelic Composition: Cxcr4^tm1Tng/Cxcr4^tm2Tng; Tg(Tek-cre)12Flv/0
• Genetic Background: involves: 129P2/OlaHsd * C3H * C57BL/6

cardiovascular system

poor arterial differentiation ( J:195048 )

abnormal skin vasculature morphology ( J:195048 )

• mice exhibit a failure of nerve-vessel alignment in developing limb skin compared with wild-type mice

• however, vascular density is normal

abnormal developmental vascular remodeling ( J:195048 )

• disorganized branching patterns in developing limb skin

abnormal vascular smooth muscle morphology ( J:195048 )

• reduced smooth muscle cell coverage of small diameter branched vessels

• however, coverage of large diameter veins is normal

nervous system

nervous system phenotype ( J:195048 )

N • mice exhibit normal innervation accompanied by migrating Schwann cells

integument

abnormal skin vasculature morphology ( J:195048 )

• mice exhibit a failure of nerve-vessel alignment in developing limb skin compared with wild-type mice

• however, vascular density is normal

muscle

abnormal vascular smooth muscle morphology ( J:195048 )

• reduced smooth muscle cell coverage of small diameter branched vessels

• however, coverage of large diameter veins is normal

Genotype
MGI:3639683

cn4

• Allelic Composition: Cd19^tm1(cre)Cgn/Cd19⁺; Cxcr4^tm1Tng/Cxcr4^tm2Tng
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

hematopoietic system

decreased plasma cell number ( J:109147 )

• the number of plasma cells in bone marrow were severely reduced

• the numbers of mature B cells and plasma cells in spleen were normal

immune system

decreased plasma cell number ( J:109147 )

• the number of plasma cells in bone marrow were severely reduced

• the numbers of mature B cells and plasma cells in spleen were normal