Phenotypes Associated with This Genotype

Genotype
MGI:3589021

• Allelic Composition: Spp1^tm1Rit/Spp1^tm1Rit
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6

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

mortality/aging

mortality/aging ( J:56535 )

N • homozygotes are viable, fertile and overtly normal with no significant differences in lactation, growth development, or organ and tissue histology

immune system

decreased osteoclast cell number ( J:115395 )

• fewer osteoclasts accumulate at the site of an implanted bone disc compared to in similarly treated wild-type mice

increased osteoclast cell number ( J:56353 , J:56535 )

• 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)

abnormal osteoclast physiology ( J:56353 , J:68872 )

• 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)

decreased interferon-gamma secretion ( J:60284 )

• 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

increased interleukin-10 secretion ( J:60284 )

• draining lymph node cells from HSV-1-infected mice produce increased IL10 compared with cells from similarly treated wild-type mice

decreased interleukin-12 secretion ( J:60284 )

• 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

increased interleukin-4 secretion ( J:60284 )

• draining lymph node cells from HSV-1-infected mice produce increased IL4 compared with cells from similarly treated wild-type mice

abnormal inflammatory response ( J:60284 )

• mice treated with polyvinyl pyrrolidone fail to exhibit a granulomatous response unlike similarly treated wild-type mice

decreased susceptibility to type IV hypersensitivity reaction ( J:60284 )

• 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

abnormal response to infection ( J:60284 )

• 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

decreased susceptibility to Herpesvirales infection ( J:60284 )

• 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

skeleton phenotype ( J:56535 )

N • homozygotes exhibit radiographically normal skeletal size and patterning

N • ultrastructurally, the cellular and extracellular matrix organization and composition of bones and teeth appears unaffected

abnormal osteoblast physiology ( J:128077 )

• calvarial osteoblasts form larger mineralized nodules compared with wild-type cells

decreased osteoclast cell number ( J:115395 )

• fewer osteoclasts accumulate at the site of an implanted bone disc compared to in similarly treated wild-type mice

increased osteoclast cell number ( J:56353 , J:56535 )

• 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)

abnormal osteoclast physiology ( J:56353 , J:68872 )

• 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)

increased bone mineral density ( J:128077 )

• phosphate and calcium deposition in bone is increased compared to in wild-type mice

increased bone mineral density of presacral vertebrae ( J:128077 )

• bone mineral density and bone volume fraction in thoracic vertebrae are increased compared to in Alpl^tm1Jlm homozygotes

increased bone mineral density of lumbar vertebrae ( J:128077 )

• bone mineral density and bone volume fraction in lumbar vertebrae are increased compared to in wild-type mice

increased trabecular bone thickness ( J:128077 )

decreased bone resorption ( J:115395 )

• resorption of an implanted bone disc is impaired regardless of whether both or either the bone disc and host are Spp1^tm1Rit homozygous compared to in similarly treated wild-type mice

• however, bone absorption is restored by exogenous Spp1

homeostasis/metabolism

increased circulating creatinine level ( J:56204 )

• following renal ischemia, mice exhibit a 2-fold increase in creatinine levels compared with similarly treated wild-type mice

increased blood urea nitrogen level ( J:56204 )

• following renal ischemia, mice exhibit a 2-fold increase in blood urea nitrogen levels compared with similarly treated wild-type mice

delayed wound healing ( J:141747 )

• 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

increased susceptibility to injury ( J:56204 )

• 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

abnormal physiological neovascularization ( J:115395 )

• 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

decreased heart weight ( J:95591 )

• mice exhibit a 10% reduction in heart weight adjusted for individual body weight compared with wild-type mice

abnormal cardiovascular system physiology ( J:95591 )

• 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

decreased cardiac muscle contractility ( J:95591 )

• 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

decreased osteoclast cell number ( J:115395 )

• fewer osteoclasts accumulate at the site of an implanted bone disc compared to in similarly treated wild-type mice

increased osteoclast cell number ( J:56353 , J:56535 )

• 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)

abnormal osteoclast physiology ( J:56353 , J:68872 )

• 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

decreased sensitivity to induced cell death ( J:95591 )

• cardiac fibroblasts exhibit reduced cell death induced by apoptotic agents thapsigargin, staurosporine, actinomycin D, and cycloheximide compared with similarly treated wild-type cells

decreased fibroblast chemotaxis ( J:106243 )

• chemotactic migration of mouse embryonic fibroblasts in a Boyden chamber is impaired compared with similarly treated wild-type cells

abnormal osteoblast physiology ( J:128077 )

• calvarial osteoblasts form larger mineralized nodules compared with wild-type cells

renal/urinary system

dilated renal tubule ( J:56204 )

• increased compared with wild-type mice following renal ischemia

renal tubular necrosis ( J:56204 )

• increased compared with wild-type mice following renal ischemia

behavior/neurological

hyporesponsive to tactile stimuli ( J:120346 )

• mechanical withdrawal threshold is increased compared to in wild-type mice

• however, allodynia is normal

nervous system

nervous system phenotype ( J:120346 )

N • adult neurite outgrowth is normal

muscle

decreased cardiac muscle contractility ( J:95591 )

• 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