Phenotypes associated with this allele

• Allele Symbol: Spp1^tm1Rit
• Allele Name: targeted mutation 1, Susan R Rittling
• Allele ID: MGI:1932084
• Summary: 9 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Spp1^tm1Rit/Spp1^tm1Rit	B6.129S7-Spp1^tm1Rit	MGI:4839087
hm2	Spp1^tm1Rit/Spp1^tm1Rit	involves: 129S7/SvEvBrd	MGI:4361681
hm3	Spp1^tm1Rit/Spp1^tm1Rit	involves: 129S7/SvEvBrd * C57BL/6	MGI:3589021
cx4	Apoe^tm1Unc/Apoe^tm1Unc Spp1^tm1Rit/Spp1^+	involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6	MGI:4361864
cx5	Apoe^tm1Unc/Apoe^tm1Unc Spp1^tm1Rit/Spp1^tm1Rit	involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6	MGI:4361863
cx6	Alpl^tm1Jlm/Alpl^tm1Jlm Spp1^tm1Rit/Spp1^tm1Rit	involves: 129S1/SvImJ * 129S2/SvPas * 129S7/SvEvBrd * C57BL/6	MGI:5787926
cx7	Aprt^tm1Jat/Aprt^tm1Jat Spp1^tm1Rit/Spp1^tm1Rit	involves: 129S2/SvPas * 129S7/SvEvBrd	MGI:4361876
cx8	Alpl^tm1Jlm/Alpl^tm1Jlm Spp1^tm1Rit/Spp1^tm1Rit	involves: 129S2/SvPas * 129S7/SvEvBrd * C57BL/6	MGI:4361902
cx9	Fas^lpr/Fas^lpr Spp1^tm1Rit/Spp1^tm1Rit	involves: 129S7/SvEvBrd * C57BL/6 * MRL/Mp	MGI:4361838

Genotype
MGI:4839087

hm1

• Allelic Composition: Spp1^tm1Rit/Spp1^tm1Rit
• Genetic Background: B6.129S7-Spp1^tm1Rit

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

liver/biliary system

abnormal liver morphology ( J:93915 )

• considerably less liver damage induced by concanavalin A injection than in controls

• as measured by alanine transaminase levels

homeostasis/metabolism

decreased physiological sensitivity to xenobiotic ( J:93915 )

• considerably less liver damage induced by concanavalin A injection than in controls

• as measured by alanine transaminase levels

immune system

decreased interferon-gamma secretion ( J:93915 )

• in the liver after concanavalin A injection relative to controls

decreased tumor necrosis factor secretion ( J:93915 )

• in the liver after concanavalin A injection relative to controls

decreased acute inflammation ( J:93915 )

• significantly reduced infiltration of neutrophiles into the liver after concanavalin A injection

Genotype
MGI:4361681

hm2

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

mortality/aging

increased susceptibility to induced morbidity/mortality ( J:117329 )

• myeoablated mice restored with wild-type hematopoietic stem cells exhibit increased lethality compared with similarly treated wild-type mice

hematopoietic system

abnormal blood cell morphology/development ( J:117329 )

• transmarrow migration of transplanted bone marrow hematopoietic stem cells is absent unlike in similarly treated wild-type mice

• myeoablated mice restored with wild-type hematopoietic stem cells exhibit increased lethality compared with similarly treated wild-type mice

• 3 months after engraftment fewer donor cells are present in the microenvironment compared to in similarly treated wild-type mice

increased bone marrow cell number ( J:117329 )

increased hematopoietic stem cell number ( J:117329 )

skeleton

increased bone mineral density ( J:81625 )

• at 16 weeks, the ratio of mineral to matrix is increased in the cortical center and area of cortical bone adjacent to the endosteum compared to in wild-type mice

abnormal bone mineralization ( J:81625 )

• crystallinity in the bones of younger mice is increased compared to in wild-type mice

Genotype
MGI:3589021

hm3

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

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

renal tubular necrosis ( J:56204 )

• increased compared with wild-type mice following renal ischemia

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

renal tubular necrosis ( J:56204 )

• increased compared with wild-type mice following renal ischemia

dilated renal tubule ( 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

Genotype
MGI:4361864

cx4

• Allelic Composition: Apoe^tm1Unc/Apoe^tm1Unc; Spp1^tm1Rit/Spp1⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6

cardiovascular system

decreased susceptibility to atherosclerosis ( J:103051 )

• atherosclerotic lesions in female mice are 43% smaller than in Apoe^tm1Unc homozygotes with reduced aortic wall inflammation

homeostasis/metabolism

increased circulating cholesterol level ( J:103051 )

• total circulating cholesterol and non-HDL-cholesterol levels are increased in male mice compared to in Apoe^tm1Unc homozygotes

increased circulating triglyceride level ( J:103051 )

• in male mice compared to in Apoe^tm1Unc homozygotes

Genotype
MGI:4361863

cx5

• Allelic Composition: Apoe^tm1Unc/Apoe^tm1Unc; Spp1^tm1Rit/Spp1^tm1Rit
• Genetic Background: involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6

cardiovascular system

decreased susceptibility to atherosclerosis ( J:103051 )

• atherosclerotic lesions in female mice are 34% smaller than in Apoe^tm1Unc homozygotes

calcified artery ( J:103051 )

• male mice exhibit increased vascular calcification of aortic root sections compared to in Apoe^tm1Unc homozygotes

homeostasis/metabolism

increased circulating cholesterol level ( J:103051 )

• total circulating cholesterol and non-HDL-cholesterol levels are increased 1.5-fold in male mice compared to in Apoe^tm1Unc homozygotes

increased circulating triglyceride level ( J:103051 )

• plasma triglyceride levels are increased 4-fold in male mice compared to in Apoe^tm1Unc homozygotes

Genotype
MGI:5787926

cx6

• Allelic Composition: Alpl^tm1Jlm/Alpl^tm1Jlm; Spp1^tm1Rit/Spp1^tm1Rit
• Genetic Background: involves: 129S1/SvImJ * 129S2/SvPas * 129S7/SvEvBrd * C57BL/6

craniofacial

abnormal tooth root development ( J:233260 )

• root dentin defects that are indistinguishable from single Alpl^tm1Jlm homozygotes

abnormal dentin morphology ( J:233260 )

• root dentin defects that are indistinguishable from single Alpl^tm1Jlm homozygotes

growth/size/body

abnormal tooth root development ( J:233260 )

• root dentin defects that are indistinguishable from single Alpl^tm1Jlm homozygotes

abnormal dentin morphology ( J:233260 )

• root dentin defects that are indistinguishable from single Alpl^tm1Jlm homozygotes

skeleton

abnormal tooth root development ( J:233260 )

• root dentin defects that are indistinguishable from single Alpl^tm1Jlm homozygotes

abnormal dentin morphology ( J:233260 )

• root dentin defects that are indistinguishable from single Alpl^tm1Jlm homozygotes

Genotype
MGI:4361876

cx7

• Allelic Composition: Aprt^tm1Jat/Aprt^tm1Jat; Spp1^tm1Rit/Spp1^tm1Rit
• Genetic Background: involves: 129S2/SvPas * 129S7/SvEvBrd

mortality/aging

postnatal lethality ( J:114314 )

• fewer than expected female pups are observed (no time point of death given)

renal/urinary system

abnormal urine nucleoside level ( J:114314 )

• at 12 weeks, purine excretion in male mice is higher than in Aprt^tm1Jat homozygotes

abnormal kidney morphology ( J:114314 )

• at 12 weeks, female mice exhibit a more severe renal pathology than Aprt^tm1Jat homozygotes

growth/size/body

abnormal body weight ( J:114314 )

• growth curve analysis indicates that female mice are smaller at young ages but exhibit rapid weight gain in order to achieve normal maximal weight

decreased body weight ( J:114314 )

• in male mice compared with Aprt^tm1Jat homozygotes

homeostasis/metabolism

abnormal urine nucleoside level ( J:114314 )

• at 12 weeks, purine excretion in male mice is higher than in Aprt^tm1Jat homozygotes

Genotype
MGI:4361902

cx8

• Allelic Composition: Alpl^tm1Jlm/Alpl^tm1Jlm; Spp1^tm1Rit/Spp1^tm1Rit
• Genetic Background: involves: 129S2/SvPas * 129S7/SvEvBrd * C57BL/6

cellular

abnormal osteoblast physiology ( J:128077 )

• calvarial osteoblasts form larger mineralized nodules compared with Alpl^tm1Jlm homozygous cells

mortality/aging

postnatal lethality, complete penetrance ( J:128077 )

• mice die within 10 to 14 days of birth

skeleton

abnormal osteoblast physiology ( J:128077 )

• calvarial osteoblasts form larger mineralized nodules compared with Alpl^tm1Jlm homozygous cells

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

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

• bone volume fraction in lumbar vertebrae are increased compared to in wild-type mice and Spp1^tm1Rit homozygotes

increased bone trabecula number ( J:128077 )

• trabecular number is greater than in Alpl^tm1Jlm homozygotes and wild-type mice

decreased bone mineralization ( J:128077 )

• mineral deposition is decreased compared to in wild-type mice

growth/size/body

decreased body weight ( J:128077 )

Genotype
MGI:4361838

cx9

• Allelic Composition: Fas^lpr/Fas^lpr; Spp1^tm1Rit/Spp1^tm1Rit
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6 * MRL/Mp

immune system

enlarged spleen ( J:73396 )

• at day 175 compared with wild-type mice with further increase at day 275 compared with Fas^lpr homozygotes

increased IgA level ( J:73396 )

• at day 275 compared with wild-type mice

• however, at day 175 IgA levels are normal unlike in Fas^lpr homozygotes

increased IgG1 level ( J:73396 )

• at day 275 compared with wild-type mice

• however, at day 175 IgG1 levels are normal unlike in Fas^lpr homozygotes

increased IgG2a level ( J:73396 )

• at day 275 compared with wild-type mice

• however, at day 175 IgG2a levels are normal unlike in Fas^lpr homozygotes

increased IgG2b level ( J:73396 )

• at day 275 compared with wild-type mice

• however, at day 175 IgG2b levels are normal unlike in Fas^lpr homozygotes

increased IgG3 level ( J:73396 )

• at day 275 compared with wild-type mice

• however, at day 175 IgG3 levels are normal unlike in Fas^lpr homozygotes

increased IgM level ( J:73396 )

• at day 275 compared with wild-type mice

• however, at day 175 IgM levels are normal unlike in Fas^lpr homozygotes

lymph node hyperplasia ( J:73396 )

• at day 175 compared with wild-type mice with further increase at day 275 compared with Fas^lpr homozygotes

increased anti-double stranded DNA antibody level ( J:73396 )

• at day 275

increased anti-single stranded DNA antibody level ( J:73396 )

• at day 275

kidney inflammation ( J:73396 )

• mice exhibit moderate nephritis that worsens from day 175 to 215 unlike either single homozygote

renal/urinary system

kidney inflammation ( J:73396 )

• mice exhibit moderate nephritis that worsens from day 175 to 215 unlike either single homozygote

hematopoietic system

enlarged spleen ( J:73396 )

• at day 175 compared with wild-type mice with further increase at day 275 compared with Fas^lpr homozygotes

increased IgA level ( J:73396 )

• at day 275 compared with wild-type mice

• however, at day 175 IgA levels are normal unlike in Fas^lpr homozygotes

increased IgG1 level ( J:73396 )

• at day 275 compared with wild-type mice

• however, at day 175 IgG1 levels are normal unlike in Fas^lpr homozygotes

increased IgG2a level ( J:73396 )

• at day 275 compared with wild-type mice

• however, at day 175 IgG2a levels are normal unlike in Fas^lpr homozygotes

increased IgG2b level ( J:73396 )

• at day 275 compared with wild-type mice

• however, at day 175 IgG2b levels are normal unlike in Fas^lpr homozygotes

increased IgG3 level ( J:73396 )

• at day 275 compared with wild-type mice

• however, at day 175 IgG3 levels are normal unlike in Fas^lpr homozygotes

increased IgM level ( J:73396 )

• at day 275 compared with wild-type mice

• however, at day 175 IgM levels are normal unlike in Fas^lpr homozygotes

growth/size/body

enlarged spleen ( J:73396 )

• at day 175 compared with wild-type mice with further increase at day 275 compared with Fas^lpr homozygotes