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Phenotypes Associated with This Genotype
Genotype
MGI:3800941
Allelic
Composition
Tnfsf11tm1Ywc/Tnfsf11tm1Ywc
Genetic
Background
involves: 129P2/OlaHsd
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tnfsf11tm1Ywc mutation (0 available); any Tnfsf11 mutation (24 available)
phenotype observed in females
phenotype observed in males
N normal phenotype

Skeletal growth abnormalities in Tnfsf11tm1Ywc/Tnfsf11tm1Ywc mice

skeleton
• optic foramina are narrower
• the skull is 87% shorter in length than normal at 1 month of age
• the chondroosseous junction and the metaphyseal periosteum are devoid of osteoclasts (J:64737)
• absent (J:65888)
• tibia diameter is increased 131% at 2 months and 137% at 3 months compared to wild-type mice
• epiphyseal growth plates lack normal columnar organization of chondrocytes and exhibit reduced proliferating zones and increased hypertrophic zones compared to in wild-type mice
• long bones exhibit limited marrow space
• mice exhibit shortened long bones of the hindlimbs compared to wild-type mice
• tibias are 68% of normal at 1 month and 65% at 2 months of age
• 77% of normal at 1 month and 74% at 2 months
• the marrow space is filled with bone and mineralized cartilage, causing a reduction in bone marrow cellularity
• overtreatment with soluble RANKL for 3 months reverses osteopetrosis and results in excessive bone resorption and bone loss leading to osteopenia
• mice exhibit very dense vertebrae and long bones
• increase in total bone volume/total volume ratio
• bones exhibit osteopetrotic features
• systematic treatment with soluble RANKL for 1 month improves the bone phenotype
• chondrocyte organization is abnormal
• chondrocyte differentiation is abnormal
• abnormally high mineralization of vertebrae and long bones

homeostasis/metabolism

immune system
• overtreatment with soluble RANKL increases the percentage of CD4+ and CD8+ single-positive and reduces the percentage of double-positive (DP) thymocytes
• severe reduction in the size of the thymus medulla
• treatment with soluble RANKL improves thymus architecture
• Langerhans cell numbers are decreased due to decreased proliferation without increased apoptosis
• the chondroosseous junction and the metaphyseal periosteum are devoid of osteoclasts (J:64737)
• absent (J:65888)
• over 70% of mice exhibit abnormal spleen microarchitecture
• mice exhibit variable degrees of defects in B cell follicle formation
• however, about 25% of mice exhibit normal marginal zone and intact B cell follicles, and all mice exhibit normal germinal center formation following immunization with the T cell-dependent antigen nitrophenol-haptenated KLH
• mice exhibit variable degrees of defects in marginal zone integrity
• however, about 25% of mice exhibit normal marginal zone and intact B cell follicles
• decrease in the percentage of total B220+ cells, including transitional and mature B cells and increase in the numbers of promyelocytes, granulocytes, and LKS multipotent progenitors in the spleen
• treatment with soluble RANKL ameliorates the splenic abnormalities and restores B cell, promyelocyte, and LKS multipotent progenitor numbers
• Peyer's patches are small and treatment with soluble RANKL results in enlargement of Peyer's patches
• while cervical lymph nodes are found in 30% of mice, they fail to form B cell follicles
• 70% of mice lack cervical lymph nodes
• mice lack peripheral lymph nodes
• however, 30% of mice exhibit cervical lymph nodes

craniofacial
• optic foramina are narrower
• the skull is 87% shorter in length than normal at 1 month of age

respiratory system
• presence of lymphoid aggregates in the lung parenchyma with a clear internal compartmentalization of both T and B cells is seen, with a further increase in size and number of lymphoid aggregates when mice are overtreated with soluble RANKL

limbs/digits/tail
• tibia diameter is increased 131% at 2 months and 137% at 3 months compared to wild-type mice
• tibias are 68% of normal at 1 month and 65% at 2 months of age

vision/eye
• optic foramina are narrower

hematopoietic system
• overtreatment with soluble RANKL increases the percentage of CD4+ and CD8+ single-positive and reduces the percentage of double-positive (DP) thymocytes
• severe reduction in the size of the thymus medulla
• treatment with soluble RANKL improves thymus architecture
• spleen shows regions of intense extramedullary hematopoiesis
• the marrow space is filled with bone and mineralized cartilage, causing a reduction in bone marrow cellularity
• decrease in the absolute number of B220+ B cells and B220+CD43+ proB cells, of monocytes, promyelocytes, granulocytes, and LKS multipotent progenitors in the bone morrow
• Langerhans cell numbers are decreased due to decreased proliferation without increased apoptosis
• the chondroosseous junction and the metaphyseal periosteum are devoid of osteoclasts (J:64737)
• absent (J:65888)
• over 70% of mice exhibit abnormal spleen microarchitecture
• mice exhibit variable degrees of defects in B cell follicle formation
• however, about 25% of mice exhibit normal marginal zone and intact B cell follicles, and all mice exhibit normal germinal center formation following immunization with the T cell-dependent antigen nitrophenol-haptenated KLH
• mice exhibit variable degrees of defects in marginal zone integrity
• however, about 25% of mice exhibit normal marginal zone and intact B cell follicles
• decrease in the percentage of total B220+ cells, including transitional and mature B cells and increase in the numbers of promyelocytes, granulocytes, and LKS multipotent progenitors in the spleen
• treatment with soluble RANKL ameliorates the splenic abnormalities and restores B cell, promyelocyte, and LKS multipotent progenitor numbers

growth/size/body

endocrine/exocrine glands
• overtreatment with soluble RANKL increases the percentage of CD4+ and CD8+ single-positive and reduces the percentage of double-positive (DP) thymocytes
• severe reduction in the size of the thymus medulla
• treatment with soluble RANKL improves thymus architecture

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
autosomal recessive osteopetrosis 2 DOID:0110943 OMIM:259710
J:233265


Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB), Gene Ontology (GO)
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last database update
03/03/2020
MGI 6.15
The Jackson Laboratory