Analysis Tools
skeleton
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• optic foramina are narrower
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• the skull is 87% shorter in length than normal at 1 month of age
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• the chondroosseous junction and the metaphyseal periosteum are devoid of osteoclasts
(J:64737)
• absent
(J:65888)
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• tibia diameter is increased 131% at 2 months and 137% at 3 months compared to wild-type mice
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• epiphyseal growth plates lack normal columnar organization of chondrocytes and exhibit reduced proliferating zones and increased hypertrophic zones compared to in wild-type mice
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• long bones exhibit limited marrow space
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• mice exhibit shortened long bones of the hindlimbs compared to wild-type mice
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short tibia
(
J:64737
)
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• tibias are 68% of normal at 1 month and 65% at 2 months of age
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• short
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• 77% of normal at 1 month and 74% at 2 months
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• the marrow space is filled with bone and mineralized cartilage, causing a reduction in bone marrow cellularity
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• overtreatment with soluble RANKL for 3 months reverses osteopetrosis and results in excessive bone resorption and bone loss leading to osteopenia
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• mice exhibit very dense vertebrae and long bones
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• increase in total bone volume/total volume ratio
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• bones exhibit osteopetrotic features
• systematic treatment with soluble RANKL for 1 month improves the bone phenotype
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• chondrocyte organization is abnormal
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• chondrocyte differentiation is abnormal
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• abnormally high mineralization of vertebrae and long bones
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homeostasis/metabolism
immune system
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• overtreatment with soluble RANKL increases the percentage of CD4+ and CD8+ single-positive and reduces the percentage of double-positive (DP) thymocytes
|
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• severe reduction in the size of the thymus medulla
• treatment with soluble RANKL improves thymus architecture
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• Langerhans cell numbers are decreased due to decreased proliferation without increased apoptosis
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• the chondroosseous junction and the metaphyseal periosteum are devoid of osteoclasts
(J:64737)
• absent
(J:65888)
|
|
• over 70% of mice exhibit abnormal spleen microarchitecture
|
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• 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
|
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• mice exhibit variable degrees of defects in marginal zone integrity
• however, about 25% of mice exhibit normal marginal zone and intact B cell follicles
|
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• 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
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• Peyer's patches are small and treatment with soluble RANKL results in enlargement of Peyer's patches
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• while cervical lymph nodes are found in 30% of mice, they fail to form B cell follicles
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• 70% of mice lack cervical lymph nodes
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• mice lack peripheral lymph nodes
• however, 30% of mice exhibit cervical lymph nodes
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craniofacial
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• optic foramina are narrower
|
|
• the skull is 87% shorter in length than normal at 1 month of age
|
respiratory system
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• 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
|
short tibia
(
J:64737
)
|
• 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 | |
