Phenotypes associated with this allele

• Allele Symbol: Tnfsf11^tm1Pngr
• Allele Name: targeted mutation 1, Josef M Penninger
• Allele ID: MGI:1859962
• Summary: 7 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Tnfsf11^tm1Pngr/Tnfsf11^tm1Pngr	involves: 129P2/OlaHsd	MGI:5013464
hm2	Tnfsf11^tm1Pngr/Tnfsf11^tm1Pngr	involves: 129P2/OlaHsd * C57BL/6	MGI:3801009
ht3	Tnfsf11^tles/Tnfsf11^tm1Pngr	involves: 129P2/OlaHsd * 129S6/SvEvTac * C57BL/6J	MGI:5307895
cx4	Cd40^tm1Kik/Cd40^tm1Kik Tnfsf11^tm1Pngr/Tnfsf11^tm1Pngr	involves: 129P2/OlaHsd	MGI:5013467
cx5	Ltbr^tm1Mmat/Ltbr^tm1Mmat Tnfsf11^tm1Pngr/Tnfsf11^tm1Pngr	involves: 129P2/OlaHsd * C57BL/6 * CBA	MGI:5013465
cx6	Tg(Bglap2-TAg)1Rkho/0 Tnfsf11^tm1Pngr/Tnfsf11^tm1Pngr	involves: 129P2/OlaHsd * FVB/N	MGI:5796171
cx7	Tg(Bglap2-TAg)1Rkho/0 Tnfsf11^tm1Pngr/Tnfsf11^+	involves: 129P2/OlaHsd * FVB/N	MGI:5796172

Genotype
MGI:5013464

hm1

• Allelic Composition: Tnfsf11^tm1Pngr/Tnfsf11^tm1Pngr
• Genetic Background: involves: 129P2/OlaHsd

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

immune system

abnormal thymus epithelium morphology ( J:173115 )

• mice exhibit reduced percentage of UEA-1+ medullary thymic epithelial cells compared with wild-type mice

• mice exhibit reduced MHC II^high and MHC II^low medullary thymic epithelial cells (mTEC) compared with wild-type mice

• reduction of MHC II^high mTEC is more prominent compared with the reduction of MHC II^low mTEC

hematopoietic system

abnormal thymus epithelium morphology ( J:173115 )

• mice exhibit reduced percentage of UEA-1+ medullary thymic epithelial cells compared with wild-type mice

• mice exhibit reduced MHC II^high and MHC II^low medullary thymic epithelial cells (mTEC) compared with wild-type mice

• reduction of MHC II^high mTEC is more prominent compared with the reduction of MHC II^low mTEC

endocrine/exocrine glands

abnormal thymus epithelium morphology ( J:173115 )

• mice exhibit reduced percentage of UEA-1+ medullary thymic epithelial cells compared with wild-type mice

• mice exhibit reduced MHC II^high and MHC II^low medullary thymic epithelial cells (mTEC) compared with wild-type mice

• reduction of MHC II^high mTEC is more prominent compared with the reduction of MHC II^low mTEC

Genotype
MGI:3801009

hm2

• Allelic Composition: Tnfsf11^tm1Pngr/Tnfsf11^tm1Pngr
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

immune system

immune system phenotype ( J:52369 )

N • despite a lack of osteoclasts and macrocytic hyperchromic anemia, mice exhibit normal osteoclast progenitors, lymphocytes, platelets, granulocytes and monocyte numbers

N • despite splenomegaly, spleen architecture is normal

abnormal immune system morphology ( J:52369 )

decreased thymus weight ( J:52369 )

thymus hypoplasia ( J:52369 )

increased spleen weight ( J:52369 )

• despite normal cellularity, spleen weight is increased compared to in wild-type mice

decreased immature B cell number ( J:52369 )

• when bone marrow is used to reconstitute a Rag1 null mouse, the number of B220+CD43-, B220+CD25+ and B220+sIgM+ B cell precursors in the bone marrow is decreased

abnormal pro-B cell differentiation ( J:52369 )

• when bone marrow is used to reconstitute a Rag1 null mouse

arrested T cell differentiation ( J:52369 )

• differentiation of CD4/CD8 double-negative CD44-CD25+ precursors to CD44-CD25- is blocked

• T cell development arrest is intrinsic as determined by bone marrow transplants

decreased mature B cell number ( J:52369 )

• the number of IgM+sIgD+ or B220+sIgM+ B cells is decreased compared to in wild-type mice

decreased osteoclast cell number ( J:52369 )

• absent

small Peyer's patches ( J:52369 )

absent mesenteric lymph nodes ( J:52369 )

absent peripheral lymph nodes ( J:52369 )

abnormal immune system physiology ( J:52369 )

decreased interferon-gamma secretion ( J:52369 )

• T cells are activated with wild-type dendritic cells or anti-CD23 and anti-CD28 antibodies, T cell IFN-gamma production is decreased compared to that of wild-type T cells

decreased interleukin-2 secretion ( J:52369 )

• T cells are activated with wild-type dendritic cells or anti-CD23 and anti-CD28 antibodies, T cell IL-2 production is decreased compared to that of wild-type T cells

decreased interleukin-4 secretion ( J:52369 )

• T cells are activated with anti-CD23 and anti-CD28 antibodies, T cell IL-4 production is decreased compared to that of wild-type T cells

decreased interleukin-5 secretion ( J:52369 )

• T cells are activated with anti-CD23 and anti-CD28 antibodies, T cell IL-5 production is decreased compared to that of wild-type T cells

decreased interleukin-6 secretion ( J:52369 )

• T cells are activated with anti-CD23 and anti-CD28 antibodies, T cell IL-6 production is decreased compared to that of wild-type T cells

skeleton

abnormal neurocranium morphology ( J:52369 )

• mice exhibit a thin calvaria and reduced marrow spaces compared to in wild-type mice

thin neurocranium ( J:52369 )

failure of tooth eruption ( J:52369 , J:64718 )

decreased osteoclast cell number ( J:52369 )

• absent

abnormal long bone epiphyseal plate morphology ( J:52369 )

• epiphysial growth plates lack the normal columnar structure of chondrocytes

decreased length of long bones ( J:52369 )

increased diameter of long bones ( J:52369 )

• at the ends

increased bone mineral density ( J:52369 )

• at 4 weeks of age, trabecular bone density in the metaphysis and total bone density in the diaphysis is increased compared to in wild-type mice

osteopetrosis ( J:52369 , J:64718 )

• evident at 2 days of age as radio-opaque long bones, vertebral bodies and ribs (J:52369)

endocrine/exocrine glands

decreased thymus weight ( J:52369 )

thymus hypoplasia ( J:52369 )

abnormal mammary gland growth during pregnancy ( J:64718 )

♀ • differentiation and expansion of alveolar buds into mature lobulo-alveolar mammary structures is completely arrested at day 14.5 of pregnancy

♀ • however, luminal expansion of epithelial ducts is normal

♀ • mammary development during pregnancy cannot be rescued by wild-type stroma

♀ • alveolar epithelial cell proliferation and survival is decreased compared to in wild-type mice

lactation failure ( J:64718 )

♀ • female mice fail to lactate and pups die within 48hrs of birth regardless of genotype

craniofacial

abnormal neurocranium morphology ( J:52369 )

• mice exhibit a thin calvaria and reduced marrow spaces compared to in wild-type mice

thin neurocranium ( J:52369 )

failure of tooth eruption ( J:52369 , J:64718 )

round face ( J:52369 )

• mice older than 6 months develop round faces

growth/size/body

failure of tooth eruption ( J:52369 , J:64718 )

round face ( J:52369 )

• mice older than 6 months develop round faces

postnatal growth retardation ( J:52369 )

• after weaning secondary to a failure of tooth eruption

increased spleen weight ( J:52369 )

• despite normal cellularity, spleen weight is increased compared to in wild-type mice

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:52369 )

N • despite osteopetrosis, mice exhibit normal serum levels of calcium, phosphorus and alkaline phosphatase at 4 weeks of age

hematopoietic system

hematopoietic system phenotype ( J:52369 )

N • despite a lack of osteoclasts and macrocytic hyperchromic anemia, mice exhibit normal osteoclast progenitors, lymphocytes, platelets, granulocytes and monocyte numbers

N • despite splenomegaly, spleen architecture is normal

decreased thymus weight ( J:52369 )

thymus hypoplasia ( J:52369 )

increased spleen weight ( J:52369 )

• despite normal cellularity, spleen weight is increased compared to in wild-type mice

decreased immature B cell number ( J:52369 )

• when bone marrow is used to reconstitute a Rag1 null mouse, the number of B220+CD43-, B220+CD25+ and B220+sIgM+ B cell precursors in the bone marrow is decreased

abnormal pro-B cell differentiation ( J:52369 )

• when bone marrow is used to reconstitute a Rag1 null mouse

arrested T cell differentiation ( J:52369 )

• differentiation of CD4/CD8 double-negative CD44-CD25+ precursors to CD44-CD25- is blocked

• T cell development arrest is intrinsic as determined by bone marrow transplants

extramedullary hematopoiesis ( J:52369 )

• in the liver and spleen

macrocytic anemia ( J:52369 )

• mice exhibit mild macrocytic hyperchromic anemia

decreased mature B cell number ( J:52369 )

• the number of IgM+sIgD+ or B220+sIgM+ B cells is decreased compared to in wild-type mice

decreased osteoclast cell number ( J:52369 )

• absent

reproductive system

abnormal mammary gland growth during pregnancy ( J:64718 )

♀ • differentiation and expansion of alveolar buds into mature lobulo-alveolar mammary structures is completely arrested at day 14.5 of pregnancy

♀ • however, luminal expansion of epithelial ducts is normal

♀ • mammary development during pregnancy cannot be rescued by wild-type stroma

♀ • alveolar epithelial cell proliferation and survival is decreased compared to in wild-type mice

integument

abnormal mammary gland growth during pregnancy ( J:64718 )

♀ • differentiation and expansion of alveolar buds into mature lobulo-alveolar mammary structures is completely arrested at day 14.5 of pregnancy

♀ • however, luminal expansion of epithelial ducts is normal

♀ • mammary development during pregnancy cannot be rescued by wild-type stroma

♀ • alveolar epithelial cell proliferation and survival is decreased compared to in wild-type mice

lactation failure ( J:64718 )

♀ • female mice fail to lactate and pups die within 48hrs of birth regardless of genotype

Genotype
MGI:5307895

ht3

• Allelic Composition: Tnfsf11^tles/Tnfsf11^tm1Pngr
• Genetic Background: involves: 129P2/OlaHsd * 129S6/SvEvTac * C57BL/6J

skeleton

failure of tooth eruption ( J:179743 )

decreased osteoclast cell number ( J:179743 )

• absent

increased bone volume ( J:179743 )

abnormal trabecular bone morphology ( J:179743 )

• trabecular spacing is reduced compared to in wild-type mice

increased bone trabecula number ( J:179743 )

increased bone mass ( J:179743 )

osteopetrosis ( J:179743 )

• severe

immune system

decreased osteoclast cell number ( J:179743 )

• absent

craniofacial

failure of tooth eruption ( J:179743 )

hematopoietic system

decreased osteoclast cell number ( J:179743 )

• absent

growth/size/body

failure of tooth eruption ( J:179743 )

Genotype
MGI:5013467

cx4

• Allelic Composition: Cd40^tm1Kik/Cd40^tm1Kik; Tnfsf11^tm1Pngr/Tnfsf11^tm1Pngr
• Genetic Background: involves: 129P2/OlaHsd

immune system

abnormal thymus epithelium morphology ( J:173115 )

• mice exhibit reduced MHC II^high and MHC II^low medullary thymic epithelial cells (mTEC) compared with wild-type mice

• mice exhibit fewer Aire+ medullary epithelial cells (mTEC) compared with wild-type mice

hematopoietic system

abnormal thymus epithelium morphology ( J:173115 )

• mice exhibit reduced MHC II^high and MHC II^low medullary thymic epithelial cells (mTEC) compared with wild-type mice

• mice exhibit fewer Aire+ medullary epithelial cells (mTEC) compared with wild-type mice

endocrine/exocrine glands

abnormal thymus epithelium morphology ( J:173115 )

• mice exhibit reduced MHC II^high and MHC II^low medullary thymic epithelial cells (mTEC) compared with wild-type mice

• mice exhibit fewer Aire+ medullary epithelial cells (mTEC) compared with wild-type mice

Genotype
MGI:5013465

cx5

• Allelic Composition: Ltbr^tm1Mmat/Ltbr^tm1Mmat; Tnfsf11^tm1Pngr/Tnfsf11^tm1Pngr
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * CBA

immune system

abnormal thymus epithelium morphology ( J:173115 )

• mice exhibit more severe reduction medullary thymic epithelial cells (mTEC) than either single homozygote

• mice exhibit fewer Aire+ medullary epithelial cells (mTEC) compared with wild-type mice

hematopoietic system

abnormal thymus epithelium morphology ( J:173115 )

• mice exhibit more severe reduction medullary thymic epithelial cells (mTEC) than either single homozygote

• mice exhibit fewer Aire+ medullary epithelial cells (mTEC) compared with wild-type mice

endocrine/exocrine glands

abnormal thymus epithelium morphology ( J:173115 )

• mice exhibit more severe reduction medullary thymic epithelial cells (mTEC) than either single homozygote

• mice exhibit fewer Aire+ medullary epithelial cells (mTEC) compared with wild-type mice

Genotype
MGI:5796171

cx6

• Allelic Composition: Tg(Bglap2-TAg)1Rkho/0; Tnfsf11^tm1Pngr/Tnfsf11^tm1Pngr
• Genetic Background: involves: 129P2/OlaHsd * FVB/N

neoplasm

decreased osteosarcoma incidence ( J:234128 )

• mice exhibit suppression of osteosarcoma development with only 2 of 35 mice showing tumors

limbs/digits/tail

abnormal femur morphology ( J:234128 )

• femurs from 42 week old mice show only benign parosteal growths without evidence of malignant cells

skeleton

abnormal femur morphology ( J:234128 )

• femurs from 42 week old mice show only benign parosteal growths without evidence of malignant cells

decreased osteosarcoma incidence ( J:234128 )

• mice exhibit suppression of osteosarcoma development with only 2 of 35 mice showing tumors

Genotype
MGI:5796172

cx7

• Allelic Composition: Tg(Bglap2-TAg)1Rkho/0; Tnfsf11^tm1Pngr/Tnfsf11⁺
• Genetic Background: involves: 129P2/OlaHsd * FVB/N

neoplasm

increased osteosarcoma incidence ( J:234128 )

• mice exhibit the same tumor incidence, burden and survival as single Tg(Bglap2-TAg)1Rkho hemizygous mice

skeleton

increased osteosarcoma incidence ( J:234128 )

• mice exhibit the same tumor incidence, burden and survival as single Tg(Bglap2-TAg)1Rkho hemizygous mice