Phenotypes associated with this allele

• Allele Symbol: Cxcr4^tm2Yzo
• Allele Name: targeted mutation 2, Yong-Rui Zou
• Allele ID: MGI:3525214
• Summary: 6 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Ctnnb1^tm1Mmt/Ctnnb1^+ Cxcr4^tm2Yzo/Cxcr4^tm2Yzo Tg(Wap-cre)11738Mam/0 Tg(Wap-Hgf)402Mig/0	FVB.Cg-Cxcr4^tm2Yzo Ctnnb1^tm1Mmt Tg(Wap-cre)11738Mam Tg(Wap-Hgf)402Mig	MGI:5576532
cn2	Cxcr4^tm2Yzo/Cxcr4^tm3.1Yzo Cd19^tm1(cre)Cgn/Cd19^+	involves: 129P2/OlaHsd	MGI:4878990
cn3	Cxcr4^tm2Yzo/Cxcr4^tm2Yzo Cd19^tm1(cre)Cgn/Cd19^+	involves: 129P2/OlaHsd	MGI:3526527
cn4	Cxcr4^tm2Yzo/Cxcr4^tm2Yzo Lyz2^tm1(cre)Ifo/Lyz2^+	involves: 129P2/OlaHsd * C57BL/6	MGI:6116482
cn5	Cxcr4^tm2Yzo/Cxcr4^tm2Yzo Tg(Fabp4-cre)1Rev/0	involves: 129P2/OlaHsd * C57BL/6	MGI:6116483
cn6	Cxcr4^tm2Yzo/Cxcr4^tm2Yzo Tg(Myh6-cre)2182Mds/0	involves: 129P2/OlaHsd * C57BL/6 * FVB/N	MGI:7261455

Genotype
MGI:5576532

cn1

• Allelic Composition: Ctnnb1^tm1Mmt/Ctnnb1⁺; Cxcr4^tm2Yzo/Cxcr4^tm2Yzo; Tg(Wap-cre)11738Mam/0; Tg(Wap-Hgf)402Mig/0
• Genetic Background: FVB.Cg-Cxcr4^tm2Yzo Ctnnb1^tm1Mmt Tg(Wap-cre)11738Mam Tg(Wap-Hgf)402Mig

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

neoplasm

decreased mammary gland tumor incidence in breeding females ( J:206839 )

♀ • appearance of mammary tumors in postpartum females is delayed compared to triple Ctnnb1^tm1Mmt Tg(Wap-cre)11738Mam Tg(Wap-Hgf)402Mig mutants, with tumors developing at 7 weeks postpartum rather than 2 weeks

♀ • tumors are smaller in females 2 weeks postpartum than in triple mutants

endocrine/exocrine glands

decreased mammary gland tumor incidence in breeding females ( J:206839 )

♀ • appearance of mammary tumors in postpartum females is delayed compared to triple Ctnnb1^tm1Mmt Tg(Wap-cre)11738Mam Tg(Wap-Hgf)402Mig mutants, with tumors developing at 7 weeks postpartum rather than 2 weeks

♀ • tumors are smaller in females 2 weeks postpartum than in triple mutants

integument

decreased mammary gland tumor incidence in breeding females ( J:206839 )

♀ • appearance of mammary tumors in postpartum females is delayed compared to triple Ctnnb1^tm1Mmt Tg(Wap-cre)11738Mam Tg(Wap-Hgf)402Mig mutants, with tumors developing at 7 weeks postpartum rather than 2 weeks

♀ • tumors are smaller in females 2 weeks postpartum than in triple mutants

Genotype
MGI:4878990

cn2

• Allelic Composition: Cxcr4^tm2Yzo/Cxcr4^tm3.1Yzo; Cd19^tm1(cre)Cgn/Cd19⁺
• Genetic Background: involves: 129P2/OlaHsd

hematopoietic system

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 but not as severely as in Cxcr4^tm1Yzo homozygotes

immune system

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 but not as severely as in Cxcr4^tm1Yzo homozygotes

Genotype
MGI:3526527

cn3

• Allelic Composition: Cxcr4^tm2Yzo/Cxcr4^tm2Yzo; Cd19^tm1(cre)Cgn/Cd19⁺
• Genetic Background: involves: 129P2/OlaHsd

hematopoietic system

abnormal B cell differentiation ( J:94911 )

• B cell precursors are found in the blood

• a large number of the B cell precursors die before they can complete the differentiation process

decreased mature B cell number ( J:94911 )

• the total number of mature B cells in the spleen is reduced to about 65% of wild-type

decreased B-1 B cell number ( J:94911 )

• the peritoneal B1 cell population is reduced in young and old mutants

decreased B-2 B cell number ( J:94911 )

• the peritoneal B2 cell population is reduced only in older mutants

decreased plasma cell number ( J:94911 )

• a greater than 20-fold reduction in the number of T cell independent antigen-specific plasma cells in the bone marrow is seen after immunization with Ficoll

• the number of antibody-secreting cells is reduced in the bone marrow and increased in the spleen 9 days after immunization, however long-term antibody production is not impaired

decreased immunoglobulin level ( J:94911 )

• basal levels of serum IG of all isotypes are reduced

immune system

abnormal B cell differentiation ( J:94911 )

• B cell precursors are found in the blood

• a large number of the B cell precursors die before they can complete the differentiation process

decreased mature B cell number ( J:94911 )

• the total number of mature B cells in the spleen is reduced to about 65% of wild-type

decreased B-1 B cell number ( J:94911 )

• the peritoneal B1 cell population is reduced in young and old mutants

decreased B-2 B cell number ( J:94911 )

• the peritoneal B2 cell population is reduced only in older mutants

decreased plasma cell number ( J:94911 )

• a greater than 20-fold reduction in the number of T cell independent antigen-specific plasma cells in the bone marrow is seen after immunization with Ficoll

• the number of antibody-secreting cells is reduced in the bone marrow and increased in the spleen 9 days after immunization, however long-term antibody production is not impaired

decreased immunoglobulin level ( J:94911 )

• basal levels of serum IG of all isotypes are reduced

abnormal Peyer's patch follicle morphology ( J:94911 )

• B cell follicles are more dispersed, frequently occur deep in the lamina propria, and some have enlarged T cell zones

Genotype
MGI:6116482

cn4

• Allelic Composition: Cxcr4^tm2Yzo/Cxcr4^tm2Yzo; Lyz2^tm1(cre)Ifo/Lyz2⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

immune system

increased neutrophil cell number ( J:217569 )

increased lymphocyte cell number ( J:217569 )

increased monocyte cell number ( J:217569 )

adipose tissue

adipose tissue phenotype ( J:217569 )

N • mice fed standard chow or a high-fat diet exhibit normal adiposity and lymphocyte numbers in white adipose tissue

growth/size/body

growth/size/body region phenotype ( J:217569 )

N • mice fed standard chow or a high-fat diet exhibit normal weight gain

hematopoietic system

increased neutrophil cell number ( J:217569 )

increased lymphocyte cell number ( J:217569 )

increased monocyte cell number ( J:217569 )

Genotype
MGI:6116483

cn5

• Allelic Composition: Cxcr4^tm2Yzo/Cxcr4^tm2Yzo; Tg(Fabp4-cre)1Rev/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

adipose tissue

increased subcutaneous adipose tissue amount ( J:217569 )

• 1.8-fold in mice fed a high-fat diet

increased total body fat amount ( J:217569 )

• 2-fold increase in mice fed a high-fat diet

increased brown adipose tissue mass ( J:217569 )

• 2-fold in mice fed a high-fat diet

increased brown fat cell size ( J:217569 )

• in mice fed a high-fat diet

increased white fat cell size ( J:217569 )

• in mice fed a high-fat diet

increased gonadal fat pad weight ( J:217569 )

• 1.6-fold in visceral (mesenteric, retroperitoneal, and gonadal) white adipose tissue mice fed a high-fat diet

increased mesenteric fat pad weight ( J:217569 )

• 1.6-fold in visceral (mesenteric, retroperitoneal, and gonadal) white adipose tissue mice fed a high-fat diet

increased retroperitoneal fat pad weight ( J:217569 )

• 1.6-fold in visceral (mesenteric, retroperitoneal, and gonadal) white adipose tissue mice fed a high-fat diet

increased white adipose tissue mass ( J:217569 )

• in mice fed a high-fat diet

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:217569 )

N • mice fed a high-fat diet exhibit normal glucose sensitivity as similarly treated wild-type mice

increased susceptibility to diet-induced obesity ( J:217569 )

• in mice fed a high-fat diet despite normal food intake

• however, mice fed standard chow exhibit normal weight

impaired adaptive thermogenesis ( J:217569 )

• cold-exposed mice fed a high-fat diet exhibit lower body temperatures compared with wild-type mice

• however, body temperature when housed at 25 degrees Celsius is normal

decreased oxygen consumption ( J:217569 )

• in mice fed a high-fat diet during the light and dark phase

• however, oxygen consumption normalized to lean body mass is normal

immune system

decreased B cell number ( J:217569 )

• in the white adipose tissue of mice fed a high-fat diet

decreased CD4-positive, alpha-beta T cell number ( J:217569 )

• 2.4-fold decrease in the white adipose tissue of mice fed a high-fat diet

increased CD8-positive, alpha-beta T cell number ( J:217569 )

• 2.6-fold increase in the white adipose tissue of mice fed a high-fat diet

abnormal macrophage cell number ( J:217569 )

• increased F4/80+CD11b+CD206-CD11c+ M1 adipose tissue macrophages in the white adipose tissue of mice fed a high-fat diet

• 2.3-fold decreased F4/80+CD11b+CD206+CD11c- M2 adipose tissue macrophages in the white adipose tissue of mice fed a high-fat diet

growth/size/body

growth/size/body region phenotype ( J:217569 )

N • mice fed standard chow or a high-fat diet exhibit normal lean mass

increased susceptibility to diet-induced obesity ( J:217569 )

• in mice fed a high-fat diet despite normal food intake

• however, mice fed standard chow exhibit normal weight

hematopoietic system

decreased B cell number ( J:217569 )

• in the white adipose tissue of mice fed a high-fat diet

decreased CD4-positive, alpha-beta T cell number ( J:217569 )

• 2.4-fold decrease in the white adipose tissue of mice fed a high-fat diet

increased CD8-positive, alpha-beta T cell number ( J:217569 )

• 2.6-fold increase in the white adipose tissue of mice fed a high-fat diet

abnormal macrophage cell number ( J:217569 )

• increased F4/80+CD11b+CD206-CD11c+ M1 adipose tissue macrophages in the white adipose tissue of mice fed a high-fat diet

• 2.3-fold decreased F4/80+CD11b+CD206+CD11c- M2 adipose tissue macrophages in the white adipose tissue of mice fed a high-fat diet

integument

increased subcutaneous adipose tissue amount ( J:217569 )

• 1.8-fold in mice fed a high-fat diet

Genotype
MGI:7261455

cn6

• Allelic Composition: Cxcr4^tm2Yzo/Cxcr4^tm2Yzo; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * FVB/N

mortality/aging

premature death ( J:289614 )

• most mice die between 12-14 months of age

cardiovascular system

perivascular fibrosis ( J:289614 )

• at 6 months, but not 2 months, mice show progressive interstitial/perivascular fibrosis

abnormal heart morphology ( J:289614 )

• hearts from 5-month-old mice have a higher number of mitochondria and these mitochondria are smaller than in controls

• however, stroke volume and cardiac output are normal and heart rate is not significantly affected

abnormal myocardial fiber morphology ( J:289614 )

• at 6 months, but not 2 months, hearts show significant cardiac myocyte hypertrophy

increased heart weight ( J:289614 )

• by 6 months of age, mice have a 15% increase in heart weight to body weight ratio and a 50% increase by 12 months of age

cardiac hypertrophy ( J:289614 )

• at 6 months, but not 2 months, hearts show significant cardiac myocyte hypertrophy

• 4-month-old mice show elevated levels of atrial natriuretic factor (ANF), a maker of cardiac hypertrophy

cardiac interstitial fibrosis ( J:289614 )

• at 6 months, but not 2 months, mice show progressive interstitial/perivascular fibrosis

decreased heart ventricle muscle contractility ( J:289614 )

• 12-month-old mice exhibit a 3-fold decline in the maximum rate of change in left ventricular pressure (dp/dt max) and a more than 2.5-fold decline in ejection fraction

• 4-month-old mice exhibit a 2.5-fold decrease in contractility and a significant decrease in ejection fraction

decreased heart left ventricle muscle contractility ( J:289614 )

decreased left ventricle systolic pressure ( J:289614 )

• mice show an increase in left ventricular end-diastolic volume and an increase in end-systolic volume, indicating a decline in systolic pressures over time

cardiomyopathy ( J:289614 )

• mice develop progressive cardiomyopathy, showing mild cardiomyopathy as early as 4 months of age

congestive heart failure ( J:289614 )

• progressive cardiac dysfunction leads to clinical hear failure by 12 months of age

growth/size/body

increased heart weight ( J:289614 )

• by 6 months of age, mice have a 15% increase in heart weight to body weight ratio and a 50% increase by 12 months of age

cardiac hypertrophy ( J:289614 )

• at 6 months, but not 2 months, hearts show significant cardiac myocyte hypertrophy

• 4-month-old mice show elevated levels of atrial natriuretic factor (ANF), a maker of cardiac hypertrophy

homeostasis/metabolism

increased physiological sensitivity to xenobiotic ( J:289614 )

• mice are more sensitive to catecholamine exposure via an acute isoproterenol challenge, showing a greater increase in ejection fraction and dp/dt max; mice show a robust response to isoproterenol and overcome their baseline deficits to eventually reach control levels, however the effect is only transient and cardiac function goes back to baseline within minutes

muscle

abnormal myocardial fiber morphology ( J:289614 )

• at 6 months, but not 2 months, hearts show significant cardiac myocyte hypertrophy

decreased heart ventricle muscle contractility ( J:289614 )

• 12-month-old mice exhibit a 3-fold decline in the maximum rate of change in left ventricular pressure (dp/dt max) and a more than 2.5-fold decline in ejection fraction

• 4-month-old mice exhibit a 2.5-fold decrease in contractility and a significant decrease in ejection fraction

decreased heart left ventricle muscle contractility ( J:289614 )

cardiomyopathy ( J:289614 )

• mice develop progressive cardiomyopathy, showing mild cardiomyopathy as early as 4 months of age

cellular

cardiac interstitial fibrosis ( J:289614 )

• at 6 months, but not 2 months, mice show progressive interstitial/perivascular fibrosis

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
cardiomyopathy		DOID:0050700		J:289614
congestive heart failure		DOID:6000		J:289614