Mouse Genome Informatics
hm
    Inpp5dtm1Rkh/Inpp5dtm1Rkh
involves: 129S1/Sv * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
skeleton
• cross sectional area and moment of inertia reduced for femurs
• slightly but significantly shorter than in controls
• extends only half as far into marrow cavity as in controls
• 2.6 fold increase in size with a large number of nuclei
• similar to condition in human Paget disease
• macrophage show increased sensitivity to M-CSF and RANKL
• two fold increase in osteoclast number in tibias at around 41 days of age
• reduced in long bones
• trabecular separation reduced
• hyperresorptive
• when cultured on whale dentin, more surface dentin is resorbed
• deeper resorptive pits generated than for controls
• osteoblast activity is normal
• diaphyseal bone strength is reduced (rigidity, ultimate moment, fracture energy)

cellular
• reduced apoptosis of osteoclasts in culture
• macrophage show increased sensitivity to M-CSF and RANKL
• greater chemotaxic response of bone marrow macrophage to stromal cell-derived factor 1

immune system
• 2.6 fold increase in size with a large number of nuclei
• similar to condition in human Paget disease
• macrophage show increased sensitivity to M-CSF and RANKL
• two fold increase in osteoclast number in tibias at around 41 days of age
• serum levels markedly increased over levels in controls
• greater chemotaxic response of bone marrow macrophage to stromal cell-derived factor 1
• 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
• 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
• greater chemotaxic response of double negative and double positive cells to stromal cell-derived factor 1
• greater chemotaxic response of progenitor CD4+ cells of the thymus to stromal cell-derived factor 1
• increased migration of spleen cells
• greater chemotaxic response of progenitor CD8+ cells of the thymus to stromal cell-derived factor 1
• hyperresorptive
• when cultured on whale dentin, more surface dentin is resorbed
• deeper resorptive pits generated than for controls
• osteoblast activity is normal

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

hematopoietic system
• greater chemotaxic response of bone marrow macrophage to stromal cell-derived factor 1
• 2.6 fold increase in size with a large number of nuclei
• similar to condition in human Paget disease
• macrophage show increased sensitivity to M-CSF and RANKL
• two fold increase in osteoclast number in tibias at around 41 days of age
• 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
• 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
• greater chemotaxic response of double negative and double positive cells to stromal cell-derived factor 1
• greater chemotaxic response of progenitor CD4+ cells of the thymus to stromal cell-derived factor 1
• increased migration of spleen cells
• greater chemotaxic response of progenitor CD8+ cells of the thymus to stromal cell-derived factor 1
• hyperresorptive
• when cultured on whale dentin, more surface dentin is resorbed
• deeper resorptive pits generated than for controls
• osteoblast activity is normal
• chemokine suppression of myeloid progenitor cells is eliminated

limbs/digits/tail
• slightly but significantly shorter than in controls

homeostasis/metabolism
• serum levels markedly increased over levels in controls
• increased interstitial lung edema relative to controls after acute lung injury induced by intratracheal peptidoglycan administration
• increased neutrophil infiltration

Mouse Models of Human Disease
OMIM IDRef(s)
Paget Disease of Bone; PDB 602080 J:78771