Phenotypes associated with this allele

• Allele Symbol: Spp1^tm1Blh
• Allele Name: targeted mutation 1, Brigid L Hogan
• Allele ID: MGI:1932083
• Summary: 18 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Spp1^tm1Blh/Spp1^tm1Blh	129S6/SvEvTac-Spp1^tm1Blh	MGI:4361701
hm2	Spp1^tm1Blh/Spp1^tm1Blh	129S/SvEv-Spp1^tm1Blh	MGI:4361711
hm3	Spp1^tm1Blh/Spp1^tm1Blh	B6.129S6(Cg)-Spp1^tm1Blh/J	MGI:3580499
hm4	Spp1^tm1Blh/Spp1^tm1Blh	B6.129S6-Spp1^tm1Blh	MGI:3758076
hm5	Spp1^tm1Blh/Spp1^tm1Blh	BKSW.129S6-Spp1^tm1Blh	MGI:4361669
hm6	Spp1^tm1Blh/Spp1^tm1Blh	involves: 129S6/SvEvTac	MGI:4361680
hm7	Spp1^tm1Blh/Spp1^tm1Blh	involves: 129S6/SvEvTac * Black Swiss	MGI:3588986
hm8	Spp1^tm1Blh/Spp1^tm1Blh	involves: 129S6/SvEvTac * C57BL/6	MGI:4361629
ht9	Spp1^tm1Blh/Spp1^+	BKSW.129S6-Spp1^tm1Blh	MGI:4361670
ht10	Spp1^tm1Blh/Spp1^+	involves: 129S6/SvEvTac * Black Swiss	MGI:4361698
cx11	Spp1^tm1Blh/Spp1^tm1Blh Umod^tm1Xrw/Umod^tm1Xrw	129S/SvEv-Spp1^tm1Blh Umod^tm1Xrw	MGI:4361714
cx12	Apoe^tm1Unc/Apoe^tm1Unc Spp1^tm1Blh/Spp1^+	involves: 129P2/OlaHsd * 129S6/SvEvTac * Black Swiss * C57BL/6J	MGI:4361697
cx13	Apoe^tm1Unc/Apoe^tm1Unc Spp1^tm1Blh/Spp1^tm1Blh	involves: 129P2/OlaHsd * 129S6/SvEvTac * Black Swiss * C57BL/6J	MGI:4361696
cx14	Dmd^mdx/Dmd^mdx Spp1^tm1Blh/Spp1^tm1Blh	involves: 129S6/SvEvTac * C57BL/6 * C57BL/10 * C57BL/10ScSn	MGI:4361735
cx15	Dmd^mdx/Y Spp1^tm1Blh/Spp1^tm1Blh	involves: 129S6/SvEvTac * C57BL/6 * C57BL/10 * C57BL/10ScSn	MGI:4361734
cx16	Mgp^tm1Kry/Mgp^tm1Kry Spp1^tm1Blh/Spp1^tm1Blh	involves: Black Swiss * C57BL/6J	MGI:3588990
cx17	Mgp^tm1Kry/Mgp^tm1Kry Spp1^tm1Blh/Spp1^+	involves: Black Swiss * C57BL/6J	MGI:3589019
cx18	Mgp^tm1Kry/Mgp^+ Spp1^tm1Blh/Spp1^tm1Blh	involves: Black Swiss * C57BL/6J	MGI:3589020

Genotype
MGI:4361701

hm1

• Allelic Composition: Spp1^tm1Blh/Spp1^tm1Blh
• Genetic Background: 129S6/SvEvTac-Spp1^tm1Blh

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

neoplasm

decreased incidence of tumors by chemical induction ( J:112122 )

• DMBA and TPA-treated mice exhibit delayed tumor development and reduced skin tumor multiplicity compared with similarly treated wild-type mice

• DMBA and TPA-treated male mice exhibit delayed development of tumor/papilloma appearance compared with similarly treated wild-type mice

• DMBA and TPA-induced tumors exhibit increased apoptosis compared to in similarly treated wild-type mice

• however, DMBA and TPA-induced cell proliferation is normal

homeostasis/metabolism

decreased incidence of tumors by chemical induction ( J:112122 )

• DMBA and TPA-treated mice exhibit delayed tumor development and reduced skin tumor multiplicity compared with similarly treated wild-type mice

• DMBA and TPA-treated male mice exhibit delayed development of tumor/papilloma appearance compared with similarly treated wild-type mice

• DMBA and TPA-induced tumors exhibit increased apoptosis compared to in similarly treated wild-type mice

• however, DMBA and TPA-induced cell proliferation is normal

Genotype
MGI:4361711

hm2

• Allelic Composition: Spp1^tm1Blh/Spp1^tm1Blh
• Genetic Background: 129S/SvEv-Spp1^tm1Blh

renal/urinary system

decreased urine chloride ion level ( J:127526 )

• urine chloride content is lower than in wild-type mice

• however, mice exhibit normal urine creatinine, calcium, magnesium, and citrate levels

decreased urine sodium level ( J:127526 )

crystalluria ( J:127526 )

• under hyperoxaluria conditions, 65% of mice exhibit small amounts of calcium crystalluria and renal calcium crystal formation unlike similarly treated wild-type mice

nephrocalcinosis ( J:127526 )

• 10% of mice exhibit calcifications in the renal papilla unlike wild-type mice

• renal epithelial cells exhibit a 3-fold increase in crystal adhesion to epithelial cells compared with wild-type cells

• 65% of mice exposed to hyperoxaluria develop renal calcinosis unlike similarly treated wild-type mice

homeostasis/metabolism

decreased urine chloride ion level ( J:127526 )

• urine chloride content is lower than in wild-type mice

• however, mice exhibit normal urine creatinine, calcium, magnesium, and citrate levels

decreased urine sodium level ( J:127526 )

crystalluria ( J:127526 )

• under hyperoxaluria conditions, 65% of mice exhibit small amounts of calcium crystalluria and renal calcium crystal formation unlike similarly treated wild-type mice

Genotype
MGI:3580499

hm3

• Allelic Composition: Spp1^tm1Blh/Spp1^tm1Blh
• Genetic Background: B6.129S6(Cg)-Spp1^tm1Blh/J

reproductive system

reproductive system phenotype ( J:99574 )

N • despite strong Spp1⁺ mRNA expression in wild-type testis cords and protein localization in the cytoplasm of Sertoli cells, testes from E13.5 homozygotes show no differences in the number or distribution of Sertoli, Leydig, or germ cells relative to wild-type testes

hematopoietic system

decreased hematocrit ( J:133795 )

• hematocrit levels in male mice are 10% to 12% lower than in wild-type mice

• however, hematocrit levels in female mice are normal

decreased hemoglobin content ( J:133795 )

• hemoglobin levels in male mice are 10% to 12% lower than in wild-type mice

• however, hemoglobin levels in female mice are normal

abnormal hematopoietic system physiology ( J:133795 )

• proliferation of cultured erythroblasts isolated from the bone marrow is less than proliferation of wild-type cells

• however, differentiation and apoptosis of erythroblasts are normal and addition of exogenous Spp1 restores erythroblast proliferation rates

Genotype
MGI:3758076

hm4

• Allelic Composition: Spp1^tm1Blh/Spp1^tm1Blh
• Genetic Background: B6.129S6-Spp1^tm1Blh

nervous system

decreased susceptibility to dopaminergic neuron neurotoxicity ( J:118432 )

• neuronal cell death in MPTP-treated homozygotes is comparable to sham-treated wildtype and significantly less than MPTP-treated wildtype, suggesting a protective effect

abnormal microglial cell morphology ( J:118432 )

• MPTP-treated mice exhibit decreased microglial cells with longer processes compared with similarly treated wild-type mice

abnormal substantia nigra morphology ( J:118432 )

• MPTP-treated homozygotes exhibit an increase in the number of microglial cells, however, MPTP-treated wildtype mice exhibited a greater increase

• numbers of GFAP-positive astrocytes increased in the MPTP-treated wildtype mice, but not in MPTP-treated homozygotes or sham-treated wildtype mice

• astrocytic processes are longer in MPTP-treated homozygotes than in both MPTP-treated wildtype and sham-treated wildtype mice

abnormal striatum morphology ( J:118432 )

• tyrosine hydroxylase (TH) positive nerve fibers in the striatum are decreased to a lesser extent in MPTP-treated homozygotes than in MPTP-treated wildtype mice

increased neuron number ( J:118432 )

• MPTP-treated mice exhibit increased neuron and TH+ fiber survival compared to in similarly treated wild-type mice

immune system

abnormal microglial cell morphology ( J:118432 )

• MPTP-treated mice exhibit decreased microglial cells with longer processes compared with similarly treated wild-type mice

decreased susceptibility to experimental autoimmune uveoretinitis ( J:116272 )

• mice exhibit decreased incidence of experimental autoimmune uveoretinitis with fewer infiltrating inflammatory cells in the vitreous, decreased granulomas, and reduced lymphocyte proliferation compared with similarly treated wild-type mice

granulomatous inflammation ( J:116272 )

• mice exhibit decreased granulomas in a model of experimental autoimmune uveoretinitis compared with similarly treated wild-type mice

hematopoietic system

abnormal microglial cell morphology ( J:118432 )

• MPTP-treated mice exhibit decreased microglial cells with longer processes compared with similarly treated wild-type mice

homeostasis/metabolism

decreased physiological sensitivity to xenobiotic ( J:118432 )

• MPTP-treated mice exhibit increased neuron and TH+ fiber survival and decreased microglial cells with longer processes compared with similarly treated wild-type mice

decreased susceptibility to dopaminergic neuron neurotoxicity ( J:118432 )

• neuronal cell death in MPTP-treated homozygotes is comparable to sham-treated wildtype and significantly less than MPTP-treated wildtype, suggesting a protective effect

cellular

decreased susceptibility to dopaminergic neuron neurotoxicity ( J:118432 )

• neuronal cell death in MPTP-treated homozygotes is comparable to sham-treated wildtype and significantly less than MPTP-treated wildtype, suggesting a protective effect

Genotype
MGI:4361669

hm5

• Allelic Composition: Spp1^tm1Blh/Spp1^tm1Blh
• Genetic Background: BKSW.129S6-Spp1^tm1Blh

immune system

abnormal immune system physiology ( J:113585 )

• the foreign body response provoked by glutaraldehyde-fixed aortic valve leaflets is diminished in quality with a 50% to 25% reduction in macrophage recruitment, a four- to five-fold increase calcification of the leaflet, and acidification of the leaflet compared to in similarly treated wild-type mice

impaired macrophage chemotaxis ( J:113585 )

• mice exhibit a 50% to 25% reduction in macrophage recruitment to a transplanted glutaraldehyde-fixed aortic valve leaflet compared to in similarly treated wild-type mice

cellular

impaired macrophage chemotaxis ( J:113585 )

• mice exhibit a 50% to 25% reduction in macrophage recruitment to a transplanted glutaraldehyde-fixed aortic valve leaflet compared to in similarly treated wild-type mice

cardiovascular system

calcified aortic valve cusp ( J:113585 )

• the foreign body response provoked by glutaraldehyde-fixed aortic valve leaflets is diminished in quality with a four- to five-fold increase calcification of the leaflet compared to in similarly treated wild-type mice

hematopoietic system

impaired macrophage chemotaxis ( J:113585 )

• mice exhibit a 50% to 25% reduction in macrophage recruitment to a transplanted glutaraldehyde-fixed aortic valve leaflet compared to in similarly treated wild-type mice

Genotype
MGI:4361680

hm6

• Allelic Composition: Spp1^tm1Blh/Spp1^tm1Blh
• Genetic Background: involves: 129S6/SvEvTac

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:3588986

hm7

• Allelic Composition: Spp1^tm1Blh/Spp1^tm1Blh
• Genetic Background: involves: 129S6/SvEvTac * Black Swiss

mortality/aging

mortality/aging ( J:46863 )

N • under normal conditions, homozygotes are viable and fertile, with no apparent defects in growth, external morphology or behavior

N • importantly, unwounded skin from homozygotes displays normal tissue architecture and cell organization in the subepithelial, middermal, and deep dermal regions; differences in dermal organization become significant only in the context of the healing process

immune system

increased lymphocyte cell number ( J:103050 )

decreased leukocyte cell number ( J:86531 )

• peritoneal exudates exhibit decreased numbers of inflammatory cells compared with wild-type exudate

• however, serum white blood cell counts are normal

decreased macrophage cell number ( J:127389 )

• mice fed a high-fat diet exhibit reduced accumulation of macrophages in adipose tissue compared with similarly treated wild-type mice

abnormal leukocyte physiology ( J:86531 )

• leukocytes from peritoneal exudates of Ang-II-stimulated mice exhibit decreased viability compared with cells from similarly treated wild-type mice

abnormal leukocyte migration ( J:86531 )

• leukocytes exhibit decreased basal and absent MCP-1-dependent migration compared with similarly treated wild-type and heterozygous cells

abnormal macrophage physiology ( J:127389 )

• microphages are hypomotile with reduced basal motility and absent MCP-1-stimulated motility unlike wild-type cells

• exogenous Spp1 only partially rescues macrophage motility

• migration of macrophages from obese mice towards stromal vascular cells is decreased compared with wild-type cells

abnormal macrophage chemotaxis ( J:140014 )

• increased numbers of macrophage in the liver after infection

• peritoneal exudate cells elevated at 72 hours after infection relative to controls

decreased circulating interleukin-6 level ( J:127389 )

• compared to in wild-type mice when fed a high-fat diet

abnormal chemokine level ( J:127389 )

• when fed a high-fat diet, plasma levels of MCP-1 (Ccl2) and PAI-1 (Serpine1) are decreased compared to in similarly treated wild-type mice

granulomatous inflammation ( J:140014 )

• overall greater burden of granulomas after infection than in controls, 3.1% of liver tissue compared to 1.1%

abnormal response to infection ( J:103013 )

• following exposure to Schistosoma mansoni eggs, pulmonary granuloma lesions formation is delayed, granuloma size is reduced at early time points but increased at later time points, and clearance is delayed compared to in similarly treated wild-type mice

• at day 75 of S. mansoni infection, granulomas are composed of mononuclear cells unlike wild-type granulomas with epithelioid morphology

• S. mansoni egg-exposed mice exhibit reduced giant cells in granulomas until day 75 when giant cell formation is increased compared to in similarly treated wild-type mice

• S. mansoni egg-exposed mice exhibit granulomas with few or no macrophages unlike in similarly treated wild-type mice

• however, T cell accumulation in S. mansoni egg granulomas is normal

abnormal susceptibility to infection ( J:140014 )

• Mycobacterium bovis persists for at least 4 weeks after infections in livers and spleens at levels 10-40X those found in controls

• bacterial loads are reduced by 12 weeks after infection

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:103140 )

N • mice exhibit normal serum and urine biochemistry

abnormal response to cardiac infarction ( J:115399 )

• following myocardial infarction, mice exhibit increased left ventricular mid-papillary circumference, lung weight, and left ventricle volume to heart weight ratio with a greater rightward shift in left ventricle pressure-volume relationship and decreases in chamber stiffness constant, myocyte length, and collagen content compared with similarly treated wild-type mice

• however, mice exhibit normal infarct size, heart weight, number of apoptotic myocytes, and survival

decreased circulating glucose level ( J:127389 )

• compared to in wild-type mice when fed a high-fat diet

decreased circulating insulin level ( J:127389 )

• compared to in wild-type mice when fed a high-fat diet

decreased circulating triglyceride level ( J:127389 )

• compared to in wild-type mice when fed a high-fat diet

decreased circulating interleukin-6 level ( J:127389 )

• compared to in wild-type mice when fed a high-fat diet

increased respiratory quotient ( J:127389 )

• when fed a high-fat diet, mice exhibit a modest increase in respiratory quotient during the 12-hour light cycle compared with similarly treated wild-type mice

• however, mice fed a high-fat diet exhibit a normal respiratory quotient when analyzed over a 24 hour period

improved glucose tolerance ( J:127389 )

• compared to in wild-type mice when fed a high-fat diet

increased insulin sensitivity ( J:127389 )

• compared to in wild-type mice when fed a high-fat diet

abnormal chemokine level ( J:127389 )

• when fed a high-fat diet, plasma levels of MCP-1 (Ccl2) and PAI-1 (Serpine1) are decreased compared to in similarly treated wild-type mice

crystalluria ( J:103140 )

• 4 weeks following hyperoxaluria induction with 1% ethylene glycol, mice exhibit CaOx monohydrate crystalluria and retention in renal tubes unlike treated wild-type mice

increased physiological sensitivity to xenobiotic ( J:108144 )

• bleomycin-treated mice exhibit an increase in the number and size of cystic epithelial lined air spaces within fibrotic areas of the lung compared to in similarly treated wild-type mice

abnormal wound healing ( J:46863 )

• at 2 weeks after dermal incisional wounding, homozygotes exhibit reduced debridement throughout the wound site, esp. in the subepithelial dermis

• in resolving wounds, the reforming matrix appears to be less organized in both the subepithelial and middermal regions

• in the subepithelial and middermal zones, the organization of collagen fibrils and fibers is less distinct

• in the deep reticular dermis, the collagen fibril diameter is significantly smaller; fibrils remain small, with a homogeneous distribution at all wound levels

• notably, homozygotes show no significant differences in tensile strength of healing incisional wounds relative to wild-type mice

abnormal vascular wound healing ( J:103050 )

• following carotid artery ligation, mice exhibit a 10-fold decrease leukocyte infiltration, decreased neointimal formation, and greater constrictive remodeling resulting in normal lumen area but decreased medial area compared with similarly treated wild-type mice

• however, cell proliferation and apoptosis during blood vessel healing is normal at 14 days

cardiovascular system

abnormal blood vessel morphology ( J:103050 )

• the collagenous matrix around blood vessels is more loosely organized compared to in wild-type mice

• however, elastic fibers surrounding blood vessels are normal

decreased susceptibility to atherosclerosis ( J:86531 )

• mice exhibit reduced Angiotensin II-induced atherosclerotic lesions compared with Apoe^tm1Unc homozygotes

• bone marrow used to repopulate irradiated Apoe^tm1Unc homozygotes confers decreased susceptibility to Ang-II-induced atherosclerosis

abnormal blood flow velocity ( J:103050 )

• blood flow at similar heart rates is decreased compared to in wild-type mice

increased heart rate ( J:103050 )

abnormal response to cardiac infarction ( J:115399 )

• following myocardial infarction, mice exhibit increased left ventricular mid-papillary circumference, lung weight, and left ventricle volume to heart weight ratio with a greater rightward shift in left ventricle pressure-volume relationship and decreases in chamber stiffness constant, myocyte length, and collagen content compared with similarly treated wild-type mice

• however, mice exhibit normal infarct size, heart weight, number of apoptotic myocytes, and survival

decreased systemic arterial blood pressure ( J:103050 )

decreased systemic arterial systolic blood pressure ( J:103050 )

abnormal blood vessel physiology ( J:103050 )

• vascular tone and compliance are increased compared to in wild-type mice

abnormal vasodilation ( J:103050 )

• blood vessels dilate rapidly at lower pressures than similarly treated wild-type vessels

abnormal vascular wound healing ( J:103050 )

• following carotid artery ligation, mice exhibit a 10-fold decrease leukocyte infiltration, decreased neointimal formation, and greater constrictive remodeling resulting in normal lumen area but decreased medial area compared with similarly treated wild-type mice

• however, cell proliferation and apoptosis during blood vessel healing is normal at 14 days

renal/urinary system

renal/urinary system phenotype ( J:103140 )

N • mice exhibit normal urine biochemistry

crystalluria ( J:103140 )

• 4 weeks following hyperoxaluria induction with 1% ethylene glycol, mice exhibit CaOx monohydrate crystalluria and retention in renal tubes unlike treated wild-type mice

respiratory system

lung cyst ( J:108144 )

• bleomycin-treated mice exhibit an increase in the number and size of cystic epithelial lined air spaces within fibrotic areas of the lung compared to in similarly treated wild-type mice

increased lung weight ( J:115399 )

• following myocardial infarction

growth/size/body

decreased lean body mass ( J:127389 )

• compared to in wild-type mice when fed a high-fat diet

lung cyst ( J:108144 )

• bleomycin-treated mice exhibit an increase in the number and size of cystic epithelial lined air spaces within fibrotic areas of the lung compared to in similarly treated wild-type mice

increased lung weight ( J:115399 )

• following myocardial infarction

hematopoietic system

increased lymphocyte cell number ( J:103050 )

decreased leukocyte cell number ( J:86531 )

• peritoneal exudates exhibit decreased numbers of inflammatory cells compared with wild-type exudate

• however, serum white blood cell counts are normal

decreased macrophage cell number ( J:127389 )

• mice fed a high-fat diet exhibit reduced accumulation of macrophages in adipose tissue compared with similarly treated wild-type mice

abnormal leukocyte physiology ( J:86531 )

• leukocytes from peritoneal exudates of Ang-II-stimulated mice exhibit decreased viability compared with cells from similarly treated wild-type mice

abnormal leukocyte migration ( J:86531 )

• leukocytes exhibit decreased basal and absent MCP-1-dependent migration compared with similarly treated wild-type and heterozygous cells

abnormal macrophage physiology ( J:127389 )

• microphages are hypomotile with reduced basal motility and absent MCP-1-stimulated motility unlike wild-type cells

• exogenous Spp1 only partially rescues macrophage motility

• migration of macrophages from obese mice towards stromal vascular cells is decreased compared with wild-type cells

abnormal macrophage chemotaxis ( J:140014 )

• increased numbers of macrophage in the liver after infection

• peritoneal exudate cells elevated at 72 hours after infection relative to controls

muscle

abnormal vasodilation ( J:103050 )

• blood vessels dilate rapidly at lower pressures than similarly treated wild-type vessels

cellular

abnormal leukocyte migration ( J:86531 )

• leukocytes exhibit decreased basal and absent MCP-1-dependent migration compared with similarly treated wild-type and heterozygous cells

abnormal macrophage chemotaxis ( J:140014 )

• increased numbers of macrophage in the liver after infection

• peritoneal exudate cells elevated at 72 hours after infection relative to controls

Genotype
MGI:4361629

hm8

• Allelic Composition: Spp1^tm1Blh/Spp1^tm1Blh
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6

immune system

decreased dendritic cell number ( J:119298 )

• mice sensitized with TNCB and challenged hapten exhibit reduced numbers of CD11c+FITC+ cells in the skin draining lymph nodes compared with similarly treated wild-type mice

abnormal immune system physiology ( J:119298 )

• 75% less injected wild-type dendritic cells enter the axillary and inguinal lymph nodes

homeostasis/metabolism

decreased physiological sensitivity to xenobiotic ( J:119298 )

• mice sensitized with TNCB and challenged hapten exhibit reduced ear swelling and reduced numbers of CD11c+FITC+ cells in the skin draining lymph nodes compared with similarly treated wild-type mice

hematopoietic system

decreased dendritic cell number ( J:119298 )

• mice sensitized with TNCB and challenged hapten exhibit reduced numbers of CD11c+FITC+ cells in the skin draining lymph nodes compared with similarly treated wild-type mice

Genotype
MGI:4361670

ht9

• Allelic Composition: Spp1^tm1Blh/Spp1⁺
• Genetic Background: BKSW.129S6-Spp1^tm1Blh

immune system

abnormal immune system physiology ( J:113585 )

• the foreign body response provoked by glutaraldehyde-fixed aortic valve leaflets is diminished in quality with a four- to five-fold increase calcification of the leaflet compared to in similarly treated wild-type mice

cardiovascular system

calcified aortic valve cusp ( J:113585 )

• the foreign body response provoked by glutaraldehyde-fixed aortic valve leaflets is diminished in quality with a four- to five-fold increase calcification of the leaflet compared to in similarly treated wild-type mice

Genotype
MGI:4361698

ht10

• Allelic Composition: Spp1^tm1Blh/Spp1⁺
• Genetic Background: involves: 129S6/SvEvTac * Black Swiss

immune system

abnormal leukocyte migration ( J:86531 )

• leukocytes exhibit decreased basal and MCP-1-dependent migration compared with similarly treated wild-type cells

cellular

abnormal leukocyte migration ( J:86531 )

• leukocytes exhibit decreased basal and MCP-1-dependent migration compared with similarly treated wild-type cells

hematopoietic system

abnormal leukocyte migration ( J:86531 )

• leukocytes exhibit decreased basal and MCP-1-dependent migration compared with similarly treated wild-type cells

Genotype
MGI:4361714

cx11

• Allelic Composition: Spp1^tm1Blh/Spp1^tm1Blh; Umod^tm1Xrw/Umod^tm1Xrw
• Genetic Background: 129S/SvEv-Spp1^tm1Blh Umod^tm1Xrw

renal/urinary system

increased urine phosphate level ( J:127526 )

• urine phosphorus and calcium phosphate content are higher than in wild-type mice

increased urine uric acid level ( J:127526 )

crystalluria ( J:127526 )

• under hyperoxaluria conditions, 95% of mice exhibit large amounts of calcium crystalluria and renal calcium crystal formation unlike similarly treated wild-type mice

• after 1 month of hyperoxaluria, 18% of mice develop large crystalline deposits at the tip of the renal papillae that can block the proximal portions of the collecting ducts unlike similarly treated wild-type mice

• following hyperoxaluria, mice develop stones unlike similarly treated wild-type mice

dilated kidney collecting duct ( J:127526 )

• in some mice after 1 month of hyperoxaluria

nephrocalcinosis ( J:127526 )

• 39% of mice exhibit calcifications in the renal papilla unlike wild-type mice

• renal epithelial cells exhibit a 3.5-fold increase in crystal adhesion to epithelial cells compared with wild-type cells

• 95% of mice exposed to hyperoxaluria develop renal calcinosis unlike similarly treated wild-type mice

renal fibrosis ( J:127526 )

• following hyperoxaluria, mice exhibit greater renal damage and fibrosis than similarly treated wild-type mice

homeostasis/metabolism

increased urine phosphate level ( J:127526 )

• urine phosphorus and calcium phosphate content are higher than in wild-type mice

increased urine uric acid level ( J:127526 )

crystalluria ( J:127526 )

• under hyperoxaluria conditions, 95% of mice exhibit large amounts of calcium crystalluria and renal calcium crystal formation unlike similarly treated wild-type mice

• after 1 month of hyperoxaluria, 18% of mice develop large crystalline deposits at the tip of the renal papillae that can block the proximal portions of the collecting ducts unlike similarly treated wild-type mice

• following hyperoxaluria, mice develop stones unlike similarly treated wild-type mice

Genotype
MGI:4361697

cx12

• Allelic Composition: Apoe^tm1Unc/Apoe^tm1Unc; Spp1^tm1Blh/Spp1⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S6/SvEvTac * Black Swiss * C57BL/6J

cardiovascular system

atherosclerotic lesions ( J:86531 )

• Angiotensin II-induced atherosclerotic lesions exhibit reduced lesion area compared to in similarly treated Apoe^tm1Unc homozygotes

Genotype
MGI:4361696

cx13

• Allelic Composition: Apoe^tm1Unc/Apoe^tm1Unc; Spp1^tm1Blh/Spp1^tm1Blh
• Genetic Background: involves: 129P2/OlaHsd * 129S6/SvEvTac * Black Swiss * C57BL/6J

cardiovascular system

decreased susceptibility to atherosclerosis ( J:86531 )

• Angiotensin II-induced atherosclerotic lesions exhibit reduced medial inflammation, lesion area, cellularity, macrophage viability, and foam cells compared to in similarly treated Apoe^tm1Unc homozygotes

• however, untreated aged male mice exhibit normal atherosclerotic lesion development

decreased susceptibility to induced aneurysm formation ( J:86531 )

• Angiotensin II-treated mice exhibit reduced abdominal aortic aneurysm incidence and diameter compared with similarly treated Apoe^tm1Unc homozygotes

immune system

abnormal macrophage physiology ( J:86531 )

• macrophage viability in Angiotensin II-treated mice is lower than in similarly treated Apoe^tm1Unc homozygotes

hematopoietic system

abnormal macrophage physiology ( J:86531 )

• macrophage viability in Angiotensin II-treated mice is lower than in similarly treated Apoe^tm1Unc homozygotes

Genotype
MGI:4361735

cx14

• Allelic Composition: Dmd^mdx/Dmd^mdx; Spp1^tm1Blh/Spp1^tm1Blh
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * C57BL/10 * C57BL/10ScSn

Reduced diaphragm and cardiac fibrosis in Dmd^mdx/Y Spp1^tm1Blh/Spp1^tm1Blh and Dmd^mdx/Dmd^mdx Spp1^tm1Blh/Spp1^tm1Blh mice compared to Dmd^mdx/Dmd^mdx mice

immune system

decreased granulocyte number ( J:150572 )

♀ • muscles contain fewer granulocytes than in Dmd^mdx homozygotes

decreased neutrophil cell number ( J:150572 )

♀ • muscles contain fewer neutrophils than in Dmd^mdx homozygotes

decreased T cell number ( J:150572 )

♀ • muscles contain fewer CD3+/Vbeta8.1/8.2+, and NKT-like cells than in Dmd^mdx homozygotes

increased T cell number ( J:150572 )

♀ • muscles contain more CD3+ T cells than in Dmd^mdx homozygotes

increased regulatory T cell number ( J:150572 )

♀ • muscles contain more CD3+CD4+ regulatory T cells than in Dmd^mdx homozygotes

muscle

abnormal muscle physiology ( J:150572 )

♀ • mice exhibit improved muscle regeneration and reduced muscle inflammation and fibrosis in the diaphragm and heart compared with Dmd^mdx homozygotes

behavior/neurological

abnormal physical strength ( J:150572 )

♀ • at 4 and 8 weeks, mice exhibit increased strength on a wire and grip test compared with Dmd^mdx homozygotes

hematopoietic system

decreased granulocyte number ( J:150572 )

♀ • muscles contain fewer granulocytes than in Dmd^mdx homozygotes

decreased neutrophil cell number ( J:150572 )

♀ • muscles contain fewer neutrophils than in Dmd^mdx homozygotes

decreased T cell number ( J:150572 )

♀ • muscles contain fewer CD3+/Vbeta8.1/8.2+, and NKT-like cells than in Dmd^mdx homozygotes

increased T cell number ( J:150572 )

♀ • muscles contain more CD3+ T cells than in Dmd^mdx homozygotes

increased regulatory T cell number ( J:150572 )

♀ • muscles contain more CD3+CD4+ regulatory T cells than in Dmd^mdx homozygotes

Genotype
MGI:4361734

cx15

• Allelic Composition: Dmd^mdx/Y; Spp1^tm1Blh/Spp1^tm1Blh
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * C57BL/10 * C57BL/10ScSn

Reduced diaphragm and cardiac fibrosis in Dmd^mdx/Y Spp1^tm1Blh/Spp1^tm1Blh and Dmd^mdx/Dmd^mdx Spp1^tm1Blh/Spp1^tm1Blh mice compared to Dmd^mdx/Dmd^mdx mice

immune system

decreased granulocyte number ( J:150572 )

♂ • muscles contain fewer granulocytes than in Dmd^mdx homozygotes

decreased neutrophil cell number ( J:150572 )

♂ • muscles contain fewer neutrophils than in Dmd^mdx homozygotes

decreased T cell number ( J:150572 )

♂ • muscles contain fewer CD3+/Vbeta8.1/8.2+, and NKT-like cells than in Dmd^mdx homozygotes

increased T cell number ( J:150572 )

♂ • muscles contain more CD3+ T cells than in Dmd^mdx homozygotes

increased regulatory T cell number ( J:150572 )

♂ • muscles contain more CD3+CD4+ regulatory T cells than in Dmd^mdx homozygotes

muscle

abnormal muscle physiology ( J:150572 )

♂ • mice exhibit improved muscle regeneration and reduced muscle inflammation and fibrosis in the diaphragm and heart compared with Dmd^mdx homozygotes

behavior/neurological

abnormal physical strength ( J:150572 )

♂ • at 4 and 8 weeks, mice exhibit increased strength on a wire and grip test compared with Dmd^mdx homozygotes

hematopoietic system

decreased granulocyte number ( J:150572 )

♂ • muscles contain fewer granulocytes than in Dmd^mdx homozygotes

decreased neutrophil cell number ( J:150572 )

♂ • muscles contain fewer neutrophils than in Dmd^mdx homozygotes

decreased T cell number ( J:150572 )

♂ • muscles contain fewer CD3+/Vbeta8.1/8.2+, and NKT-like cells than in Dmd^mdx homozygotes

increased T cell number ( J:150572 )

♂ • muscles contain more CD3+ T cells than in Dmd^mdx homozygotes

increased regulatory T cell number ( J:150572 )

♂ • muscles contain more CD3+CD4+ regulatory T cells than in Dmd^mdx homozygotes

Genotype
MGI:3588990

cx16

• Allelic Composition: Mgp^tm1Kry/Mgp^tm1Kry; Spp1^tm1Blh/Spp1^tm1Blh
• Genetic Background: involves: Black Swiss * C57BL/6J

mortality/aging

premature death ( J:79746 )

• on average, double homozygotes die significantly earlier (4.4 0.2 weeks) than single Mgp^tm1Kry homozygotes (6.6 1.0 weeks) as a result of increased vascular calcification

• accelerated vascular calcification correlates with accelerated vascular rupture, subsequent hemorrhage and increaed mortality

cardiovascular system

abnormal aorta morphology ( J:79746 )

calcified artery ( J:79746 )

• relative to single Mgp^tm1Kry homozygotes, double homozygotes exhibit an accelerated and enhanced medial calcification of their aortae, with a ~2-fold and a >3-fold increase in calcification noted at 2 weeks and 4 weeks, respectively

• calcification initiates in the arterial media in association with elastic lamina, and progresses to fully mineralized media, mild to moderate intimal and medial thickening, fragmentation of elastic laminae, and arterial wall rupture

aneurysm ( J:79746 )

• arterial calcification ultimately results in aneurysm formation in calcified vessels

internal hemorrhage ( J:79746 )

• similar to Mgp^tm1Kry single homozygotes, double homozygotes exhibit vascular rupture and subsequent hemorrhage as a result of severe vascular calcification

Genotype
MGI:3589019

cx17

• Allelic Composition: Mgp^tm1Kry/Mgp^tm1Kry; Spp1^tm1Blh/Spp1⁺
• Genetic Background: involves: Black Swiss * C57BL/6J

mortality/aging

premature death ( J:79746 )

• mice homozygous for Mgp^tm1Kry and heterozygous for Spp1^tm1Blh start to die during weeks 3 and 4 after birth as a result of vascular rupture and subsequent internal hemorrhage

cardiovascular system

calcified artery ( J:79746 )

internal hemorrhage ( J:79746 )

Genotype
MGI:3589020

cx18

• Allelic Composition: Mgp^tm1Kry/Mgp⁺; Spp1^tm1Blh/Spp1^tm1Blh
• Genetic Background: involves: Black Swiss * C57BL/6J

mortality/aging

premature death ( J:79746 )

• mice heterozygous for Mgp^tm1Kry and homozygous for Spp1^tm1Blh start to die during weeks 3 and 4 after birth as a result of vascular rupture and subsequent internal hemorrhage

cardiovascular system

calcified artery ( J:79746 )

• ~30% of mice heterozygous for Mgp^tm1Kry and homozygous for Spp1^tm1Blh exhibit overt vascular calcification at 4-8 weeks

• in contrast, mice heterozygous for Mgp^tm1Kry and homozygous for wild-type Spp1 do NOT exhibit vascular calcification at any time point examined

internal hemorrhage ( J:79746 )