Phenotypes Associated with This Genotype

Genotype
MGI:5319308

• Allelic Composition: Inpp5d^tm1Rkh/Inpp5d^tm1Rkh
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

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

skeleton

abnormal skeleton morphology ( J:78771 )

abnormal long bone morphology ( J:78771 )

• cross sectional area and moment of inertia reduced for femurs

short femur ( J:78771 )

• slightly but significantly shorter than in controls

abnormal long bone metaphysis morphology ( J:78771 )

• extends only half as far into marrow cavity as in controls

abnormal bone structure ( J:78771 )

abnormal osteoclast morphology ( J:78771 )

• 2.6 fold increase in size with a large number of nuclei

• similar to condition in human Paget disease

abnormal osteoclast differentiation ( J:78771 )

• macrophage show increased sensitivity to M-CSF and RANKL

increased osteoclast cell number ( J:78771 )

• two fold increase in osteoclast number in tibias at around 41 days of age

decreased bone mineral density ( J:78771 )

• reduced in long bones

decreased compact bone thickness ( J:78771 )

abnormal trabecular bone morphology ( J:78771 )

• trabecular separation reduced

decreased trabecular bone volume ( J:78771 )

• reduced by 1/3

decreased bone trabecula number ( J:78771 )

decreased trabecular bone thickness ( J:78771 )

abnormal skeleton physiology ( J:78771 )

abnormal osteoclast physiology ( J:78771 )

• hyperresorptive

• when cultured on whale dentin, more surface dentin is resorbed

• deeper resorptive pits generated than for controls

• osteoblast activity is normal

decreased bone strength ( J:78771 )

• diaphyseal bone strength is reduced (rigidity, ultimate moment, fracture energy)

cellular

decreased apoptosis ( J:78771 )

• reduced apoptosis of osteoclasts in culture

abnormal osteoclast differentiation ( J:78771 )

• macrophage show increased sensitivity to M-CSF and RANKL

abnormal macrophage chemotaxis ( J:110864 )

• greater chemotaxic response of bone marrow macrophage to stromal cell-derived factor 1

enhanced B cell migration ( J:110864 )

• greater chemotaxic response of bone marrow B cells to stromal cell-derived factor 1

• increased migration of spleen cells

• enhanced migration response to B-lymphocyte chemoattractant

increased mast cell degranulation ( J:120426 )

• bone marrow mast cells primed with anti-dinitrophenyl IgE and cross-linked with DNP-human serum albumin lose 80% of granule content

• intracellular Calcium increases more than in controls

immune system

abnormal osteoclast morphology ( J:78771 )

• 2.6 fold increase in size with a large number of nuclei

• similar to condition in human Paget disease

abnormal osteoclast differentiation ( J:78771 )

• macrophage show increased sensitivity to M-CSF and RANKL

increased osteoclast cell number ( J:78771 )

• two fold increase in osteoclast number in tibias at around 41 days of age

increased circulating interleukin-6 level ( J:78771 )

• serum levels markedly increased over levels in controls

abnormal cell-mediated immunity ( J:110864 )

abnormal macrophage chemotaxis ( J:110864 )

• greater chemotaxic response of bone marrow macrophage to stromal cell-derived factor 1

enhanced B cell migration ( J:110864 )

• greater chemotaxic response of bone marrow B cells to stromal cell-derived factor 1

• increased migration of spleen cells

• enhanced migration response to B-lymphocyte chemoattractant

increased mast cell degranulation ( J:120426 )

• bone marrow mast cells primed with anti-dinitrophenyl IgE and cross-linked with DNP-human serum albumin lose 80% of granule content

• intracellular Calcium increases more than in controls

abnormal T cell physiology ( J:110864 )

• greater chemotaxic response of double negative and double positive cells to stromal cell-derived factor 1

abnormal CD4-positive, alpha-beta T cell physiology ( J:110864 )

• greater chemotaxic response of progenitor CD4+ cells of the thymus to stromal cell-derived factor 1

• increased migration of spleen cells

abnormal CD8-positive, alpha-beta T cell physiology ( J:110864 )

• greater chemotaxic response of progenitor CD8+ cells of the thymus to stromal cell-derived factor 1

abnormal osteoclast physiology ( J:78771 )

• hyperresorptive

• when cultured on whale dentin, more surface dentin is resorbed

• deeper resorptive pits generated than for controls

• osteoblast activity is normal

respiratory system

pulmonary edema ( J:100868 )

• increased interstitial lung edema relative to controls after acute lung injury induced by intratracheal peptidoglycan administration

• increased neutrophil infiltration

hematopoietic system

abnormal macrophage chemotaxis ( J:110864 )

• greater chemotaxic response of bone marrow macrophage to stromal cell-derived factor 1

enhanced B cell migration ( J:110864 )

• greater chemotaxic response of bone marrow B cells to stromal cell-derived factor 1

• increased migration of spleen cells

• enhanced migration response to B-lymphocyte chemoattractant

increased mast cell degranulation ( J:120426 )

• bone marrow mast cells primed with anti-dinitrophenyl IgE and cross-linked with DNP-human serum albumin lose 80% of granule content

• intracellular Calcium increases more than in controls

abnormal osteoclast morphology ( J:78771 )

• 2.6 fold increase in size with a large number of nuclei

• similar to condition in human Paget disease

abnormal osteoclast differentiation ( J:78771 )

• macrophage show increased sensitivity to M-CSF and RANKL

increased osteoclast cell number ( J:78771 )

• two fold increase in osteoclast number in tibias at around 41 days of age

abnormal T cell physiology ( J:110864 )

• greater chemotaxic response of double negative and double positive cells to stromal cell-derived factor 1

abnormal CD4-positive, alpha-beta T cell physiology ( J:110864 )

• greater chemotaxic response of progenitor CD4+ cells of the thymus to stromal cell-derived factor 1

• increased migration of spleen cells

abnormal CD8-positive, alpha-beta T cell physiology ( J:110864 )

• greater chemotaxic response of progenitor CD8+ cells of the thymus to stromal cell-derived factor 1

abnormal osteoclast physiology ( J:78771 )

• hyperresorptive

• when cultured on whale dentin, more surface dentin is resorbed

• deeper resorptive pits generated than for controls

• osteoblast activity is normal

abnormal bone marrow cell physiology ( J:110864 )

• chemokine suppression of myeloid progenitor cells is eliminated

limbs/digits/tail

short femur ( J:78771 )

• slightly but significantly shorter than in controls

homeostasis/metabolism

increased circulating interleukin-6 level ( J:78771 )

• serum levels markedly increased over levels in controls

pulmonary edema ( J:100868 )

• increased interstitial lung edema relative to controls after acute lung injury induced by intratracheal peptidoglycan administration

• increased neutrophil infiltration

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Paget's disease of bone		DOID:5408	OMIM:PS167250	J:78771