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Phenotypes Associated with This Genotype
Genotype
MGI:3589021
Allelic
Composition
Spp1tm1Rit/Spp1tm1Rit
Genetic
Background
involves: 129S7/SvEvBrd * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Spp1tm1Rit mutation (5 available); any Spp1 mutation (16 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
N
• homozygotes are viable, fertile and overtly normal with no significant differences in lactation, growth development, or organ and tissue histology

immune system
• fewer osteoclasts accumulate at the site of an implanted bone disc compared to in similarly treated wild-type mice
• homozygotes exhibit a 3-fold increase in osteoclast number relative to wild-type mice; ovariectomy does not increase the number of osteoclasts significantly (J:56353)
in vitro, several-fold more osteoclasts are generated in co-culture systems with wild-type calvarial osteoblast cells by using spleen cells (3- to 13-fold) or bone marrow cells (~2- to 4-fold) from homozygous mutant mice compared with wild-type mice (J:56535)
• in contrast to wild-type mice, homozygotes are resistant to ovariectomy-induced bone resorption despite a comparable reduction in uterine weight (25-30%) (J:56353)
• ovariectomized homozygotes exhibit a 12% reduction in trabecular bone volume in the absence of increased bone formation, whereas ovariectomized wild-type mice show a 58% reduction in trabecular bone volume along with a 73% increase in bone formation (J:56353)
• bone resorption and osteoclast formation induced by PTH in cultured mouse calvariae are absent in calvariae from homozygous mutant mice (J:68872)
• following treatment with polyvinyl pyrrolidone, mice exhibit a 90% reduction in IL12 production compared with in similarly treated wild-type mice
• splenocytes from L. monocytogenes infected mice produce less IFN-gamma when restimulated with heat-killed bacteria compared with similarly treated wild-type mice
• draining lymph node cells from HSV-1-infected mice produce increased IL10 compared with cells from similarly treated wild-type mice
• following treatment with polyvinyl pyrrolidone, mice exhibit a 95% reduction in IL12 production compared with in similarly treated wild-type mice
• draining lymph node cells and splenocytes from HSV-1-infected mice produce decreased IL12 compared with cells from similarly treated wild-type mice
• draining lymph node cells from HSV-1-infected mice produce increased IL4 compared with cells from similarly treated wild-type mice
• mice treated with polyvinyl pyrrolidone fail to exhibit a granulomatous response unlike similarly treated wild-type mice
• mice infected with HSV-1 do not display a tuberculin-type delayed-type hypersensitivity when challenged with HSV-1 unlike similarly treated wild-type mice
• clearance of Listeria monocytogenes is defective compared to in similarly treated wild-type mice
• splenocytes from L. monocytogenes infected mice produce less IFN-gamma when restimulated with heat-killed bacteria compared with similarly treated wild-type mice
• mice infected with HSV-1 do not display a tuberculin-type delayed-type hypersensitivity when challenged with HSV-1 unlike similarly treated wild-type mice
• corneal HSV-1 infection fails to trigger herpes simplex keratitis unlike in similarly treated wild-type mice

skeleton
N
• homozygotes exhibit radiographically normal skeletal size and patterning
• ultrastructurally, the cellular and extracellular matrix organization and composition of bones and teeth appears unaffected
• calvarial osteoblasts form larger mineralized nodules compared with wild-type cells
• fewer osteoclasts accumulate at the site of an implanted bone disc compared to in similarly treated wild-type mice
• homozygotes exhibit a 3-fold increase in osteoclast number relative to wild-type mice; ovariectomy does not increase the number of osteoclasts significantly (J:56353)
in vitro, several-fold more osteoclasts are generated in co-culture systems with wild-type calvarial osteoblast cells by using spleen cells (3- to 13-fold) or bone marrow cells (~2- to 4-fold) from homozygous mutant mice compared with wild-type mice (J:56535)
• in contrast to wild-type mice, homozygotes are resistant to ovariectomy-induced bone resorption despite a comparable reduction in uterine weight (25-30%) (J:56353)
• ovariectomized homozygotes exhibit a 12% reduction in trabecular bone volume in the absence of increased bone formation, whereas ovariectomized wild-type mice show a 58% reduction in trabecular bone volume along with a 73% increase in bone formation (J:56353)
• bone resorption and osteoclast formation induced by PTH in cultured mouse calvariae are absent in calvariae from homozygous mutant mice (J:68872)
• phosphate and calcium deposition in bone is increased compared to in wild-type mice
• bone marrow density and bone volume fraction in thoracic vertebrae are increased compared to in Alpltm1Jlm homozygotes
• bone marrow density and bone volume fraction in lumbar vertebrae are increased compared to in wild-type mice
• resorption of an implanted bone disc is impaired regardless of whether both or either the bone disc and host are Spp1tm1Rit homozygous compared to in similarly treated wild-type mice
• however, bone absorption is restored by exogenous Spp1

homeostasis/metabolism
• following renal ischemia, mice exhibit a 2-fold increase in creatinine levels compared with similarly treated wild-type mice
• following renal ischemia, mice exhibit a 2-fold increase in blood urea nitrogen levels compared with similarly treated wild-type mice
• following lens injury, mice exhibit a delay in the epithelial to mesenchymal transition of lens epithelial cells with increased cell proliferation at day 1 and 2 compared with similarly treated wild-type mice
• following renal ischemia, mice exhibit a 2-fold increase in blood urea nitrogen and creatinine levels and more extensive kidney damage with increased tubular dilation, obstruction, necrosis, and calcifications compared with similarly treated wild-type mice

cardiovascular system
• vascularization of implanted bone discs is reduced compared to in similarly treated wild-type mice
• length and branching of vessels formed during neovascularization of implanted bone discs are 3-fold less than in similarly treated wild-type mice
• mice exhibit a 10% reduction in heart weight adjusted for individual body weight compared with wild-type mice
• following treatment with hydrogen peroxide, cardiac fibroblasts exhibit increased permeability to propidium iodide (PI), decreased TUNEL-staining, and morphologies indicative of cell necrosis unlike in cardiac fibroblasts from similarly treated wild-type mice
• pretreatment with caspase-3 inhibitor decreases TUNEL staining by 30% compared to 4-fold in cardiac fibroblasts from similarly treated wild-type mice
• pretreatment with caspase-3 inhibitor fails to decreased PI staining unlike in cardiac fibroblasts from similarly treated wild-type mice
• cardiac fibroblasts exhibit reduced cell death induced by apoptotic agents thapsigargin, staurosporine, actinomycin D, and cycloheximide compared with similarly treated wild-type cells
• percent ejection fraction is decreased compared to in wild-type mice
• ex vivo analysis of cardiac function in Langendorff preparations indicate reduced contractile ability compared with wild-type mice

hematopoietic system
• fewer osteoclasts accumulate at the site of an implanted bone disc compared to in similarly treated wild-type mice
• homozygotes exhibit a 3-fold increase in osteoclast number relative to wild-type mice; ovariectomy does not increase the number of osteoclasts significantly (J:56353)
in vitro, several-fold more osteoclasts are generated in co-culture systems with wild-type calvarial osteoblast cells by using spleen cells (3- to 13-fold) or bone marrow cells (~2- to 4-fold) from homozygous mutant mice compared with wild-type mice (J:56535)
• in contrast to wild-type mice, homozygotes are resistant to ovariectomy-induced bone resorption despite a comparable reduction in uterine weight (25-30%) (J:56353)
• ovariectomized homozygotes exhibit a 12% reduction in trabecular bone volume in the absence of increased bone formation, whereas ovariectomized wild-type mice show a 58% reduction in trabecular bone volume along with a 73% increase in bone formation (J:56353)
• bone resorption and osteoclast formation induced by PTH in cultured mouse calvariae are absent in calvariae from homozygous mutant mice (J:68872)

cellular
• cardiac fibroblasts exhibit reduced cell death induced by apoptotic agents thapsigargin, staurosporine, actinomycin D, and cycloheximide compared with similarly treated wild-type cells
• increased compared with wild-type mice following renal ischemia
• chemotactic migration of mouse embryonic fibroblasts in a Boyden chamber is impaired compared with similarly treated wild-type cells
• calvarial osteoblasts form larger mineralized nodules compared with wild-type cells

renal/urinary system
• increased compared with wild-type mice following renal ischemia
• increased compared with wild-type mice following renal ischemia

behavior/neurological
• mechanical withdrawal threshold is increased compared to in wild-type mice
• however, allodynia is normal

nervous system
N
• adult neurite outgrowth is normal

muscle
• percent ejection fraction is decreased compared to in wild-type mice
• ex vivo analysis of cardiac function in Langendorff preparations indicate reduced contractile ability compared with wild-type mice

integument
• mechanical withdrawal threshold is increased compared to in wild-type mice
• however, allodynia is normal


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
08/06/2019
MGI 6.14
The Jackson Laboratory