Phenotypes associated with this allele

• Allele Symbol: Mgp^tm1Kry
• Allele Name: targeted mutation 1, Gerard Karsenty
• Allele ID: MGI:1934912
• Summary: 6 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Mgp^tm1Kry/Mgp^tm1Kry	involves: 129S7/SvEvBrd	MGI:5556193
hm2	Mgp^tm1Kry/Mgp^tm1Kry	involves: 129S7/SvEvBrd * C57BL/6J	MGI:2183282
cx3	Eln^tm1Dyl/Eln^+ Mgp^tm1Kry/Mgp^tm1Kry	involves: 129S1/Sv * 129S7/SvEvBrd * 129X1/SvJ	MGI:5556199
cx4	Mgp^tm1Kry/Mgp^tm1Kry Spp1^tm1Blh/Spp1^tm1Blh	involves: Black Swiss * C57BL/6J	MGI:3588990
cx5	Mgp^tm1Kry/Mgp^tm1Kry Spp1^tm1Blh/Spp1^+	involves: Black Swiss * C57BL/6J	MGI:3589019
cx6	Mgp^tm1Kry/Mgp^+ Spp1^tm1Blh/Spp1^tm1Blh	involves: Black Swiss * C57BL/6J	MGI:3589020

Genotype
MGI:5556193

hm1

• Allelic Composition: Mgp^tm1Kry/Mgp^tm1Kry
• Genetic Background: involves: 129S7/SvEvBrd

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

cellular

abnormal osteoblast physiology ( J:203924 )

• osteoblast function is impaired

• 2-fold increase of deposited minerals are seen in calvarial osteoblast cultures

growth/size/body

decreased body size ( J:203924 )

slow postnatal weight gain ( J:203924 )

• poor weight gain during the post-weaning period

cardiovascular system

abnormal artery morphology ( J:203924 )

• abnormal thickening and excessive branching of arteries in the lumbar vertebrae

calcified artery ( J:203924 )

• severe vascular calcification is seen at 5 weeks of age

homeostasis/metabolism

increased circulating osteocalcin level ( J:203924 )

• mild but significant increase in serum levels of osteocalcin

skeleton

decreased bone volume ( J:203924 )

• almost 25% decrease in vertebral bone volume

decreased bone trabecula number ( J:203924 )

decreased trabecular bone thickness ( J:203924 )

• reduction of trabecular thickness in vertebrae at 5 weeks of age

decreased bone mass ( J:203924 )

decreased compact bone mass ( J:203924 )

• at 5 weeks of age

decreased trabecular bone mass ( J:203924 )

• at 5 weeks of age

abnormal epiphyseal plate morphology ( J:203924 )

• premature calcification of the growth plate cartilages in the long bones and vertebrae

decreased bone ossification ( J:203924 )

• decrease in mineral apposition rate and bone formation rate/bone surface ratio, indicating reduction in bone formation

abnormal bone remodeling ( J:203924 )

• bone volume/tissue volume ratio (BV/TV) and trabecular numbers are reduced, indicating abnormal bone remodeling

abnormal osteoblast physiology ( J:203924 )

• osteoblast function is impaired

• 2-fold increase of deposited minerals are seen in calvarial osteoblast cultures

Genotype
MGI:2183282

hm2

• Allelic Composition: Mgp^tm1Kry/Mgp^tm1Kry
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6J

mortality/aging

premature death ( J:38867 )

• homozygotes develop to term but die by 2 months of age from rupture and subsequent hemorrhage of the thoracic and abdominal aorta

cardiovascular system

abnormal aorta tunica media morphology ( J:38867 )

• at 2 and 3 weeks of age, homozygotes show extensive calcification of the elastic lamellae in the media of the aortic wall as well as disrupted tissue architecture

• affected aortae exhibit cartilaginous metaplasia, typified by the presence of chondrocytes and metachromatic cartilage matrix

• in the media, chondrocytes are surrounded by hyaline cartilage and type II collagen fibrils, proteoglycans and matrix vesicles

abnormal aorta elastic fiber morphology ( J:38867 )

• affected aortae exhibit extensive calcification of elastic fibers and collagen fibrils in the media of the aortic wall

• the inorganic material found in elastic lamellae is identified as apatite

abnormal aorta smooth muscle morphology ( J:38867 )

• in affected aortae, smooth muscle cells fail to retain their spatial arrangement as discrete, contiguous layers throughout the vessel wall

calcified artery ( J:38867 )

• at 2 and 3 weeks of age, homozygotes show widespread calcification along the aorta and its branches as well as in the coronary arteries; no calcification is detected up to 1 week of age

• calcification originates at several sites and involves all elastic and muscular arteries, but not arterioles, capillaries or veins

• however, no fatty streaks or atherosclerotic plaques are observed in affected arteries

calcified aorta ( J:38867 )

• at 2 and 3 weeks of age, homozygotes show widespread calcification along the aorta and its branches

abnormal kidney vasculature morphology ( J:176031 )

• kidneys are more vascularized than controls

• renal vasculature exhibits excessive branching of small vessels, irregular caliber of arteries, and evidence of arteriovenous malformations

• kidney vessels are enlarged

• some mutants exhibit enlarged niduses and entangled vessels in the kidneys

abnormal glomerular capillary morphology ( J:176031 )

• total capillary density and the number of capillaries with a diameter of more than 20 um is increased in glomeruli

abnormal lung vasculature morphology ( J:176031 )

• pulmonary vasculature exhibits excessive branching of small vessels, irregular caliber of arteries, and evidence of arteriovenous malformations

• lung vessels are enlarged

• some mutants exhibit enlarged niduses and entangled vessels in the lungs

arteriovenous malformation ( J:176031 )

• mutants exhibit pulmonary and renal arteriovenous malformations

• presence of renal and pulmonary arteriovenous shunts

• mutants exhibit abnormal arteriovenous connections in the glomeruli, direct connections between an arterial segment and a venous segment are seen on the surface of the lungs and both afferent and efferent arterioles are seen in the kidneys

pulmonary arteriovenous malformation ( J:176031 )

• mutants exhibit pulmonary arteriovenous malformations and shunts

calcified aortic valve ( J:38867 )

• at 2 and 3 weeks of age, homozygotes exhibit calcification in coronary arteries and aortic valves but not in the myocardium

internal hemorrhage ( J:38867 )

• homozygotes die from rupture and subsequent hemorrhage of the thoracic and abdominal aorta

increased heart rate ( J:38867 )

• beginning at 2 weeks of age, homozygotes display a significantly faster heart rate than wild-type mice

growth/size/body

decreased body height ( J:38867 )

• starting at 2 weeks of age, homozygotes exhibit a shorter stature relative to wild-type mice

• at death, homozygotes are noticeably shorter than wild-type mice

postnatal growth retardation ( J:38867 )

• homozygotes exhibit a normal body size up to 2-3 weeks of age, but grow slowly thereafter

increased kidney weight ( J:176031 )

• kidneys are heavier when normalized to total body weight

skeleton

abnormal tracheal cartilage morphology ( J:38867 )

• homozygotes display inappropriate calcification of cartilage in the lower end of the trachea

abnormal long bone epiphyseal plate morphology ( J:38867 )

• at 8 weeks, homozygotes display inappropriate calcification of the growth-plate cartilage

abnormal long bone epiphyseal plate proliferative zone ( J:38867 )

• at 8 weeks, calcification of the growth plate abnormally extends into the zone of proliferating chondrocytes

• mutant proliferating chondrocytes are not organized in columns as in wild-type growth plate

decreased width of hypertrophic chondrocyte zone ( J:38867 )

• abnormal calcification of the growth plate cartilage results in the absence of hypertrophic chondorcytes

decreased bone mineral density ( J:38867 )

• abnormal calcification of the growth-plate cartilage leads to osteopenia and fractures

respiratory system

abnormal lung morphology ( J:176031 )

• mutants exhibit a paucity of terminal airways

abnormal lung vasculature morphology ( J:176031 )

• pulmonary vasculature exhibits excessive branching of small vessels, irregular caliber of arteries, and evidence of arteriovenous malformations

• lung vessels are enlarged

• some mutants exhibit enlarged niduses and entangled vessels in the lungs

small lung ( J:176031 )

• lungs are slightly smaller

abnormal bronchial cartilage morphology ( J:38867 )

• homozygotes display inappropriate calcification of cartilage in the main bronchi

abnormal tracheal cartilage morphology ( J:38867 )

• homozygotes display inappropriate calcification of cartilage in the lower end of the trachea

muscle

abnormal aorta smooth muscle morphology ( J:38867 )

• in affected aortae, smooth muscle cells fail to retain their spatial arrangement as discrete, contiguous layers throughout the vessel wall

renal/urinary system

abnormal kidney vasculature morphology ( J:176031 )

• kidneys are more vascularized than controls

• renal vasculature exhibits excessive branching of small vessels, irregular caliber of arteries, and evidence of arteriovenous malformations

• kidney vessels are enlarged

• some mutants exhibit enlarged niduses and entangled vessels in the kidneys

increased kidney weight ( J:176031 )

• kidneys are heavier when normalized to total body weight

abnormal renal glomerulus morphology ( J:176031 )

• kidneys show more glomeruli per microscopic field than controls

• mutants exhibit abnormal arteriovenous connections in the glomeruli

abnormal glomerular capillary morphology ( J:176031 )

• total capillary density and the number of capillaries with a diameter of more than 20 um is increased in glomeruli

small kidney ( J:176031 )

• kidneys are slightly smaller

Genotype
MGI:5556199

cx3

• Allelic Composition: Eln^tm1Dyl/Eln⁺; Mgp^tm1Kry/Mgp^tm1Kry
• Genetic Background: involves: 129S1/Sv * 129S7/SvEvBrd * 129X1/SvJ

cardiovascular system

calcified artery ( J:203924 )

• progression of arterial calcification is delayed compared to single Mgp homozygotes

skeleton

abnormal epiphyseal plate morphology ( J:203924 )

• vertebral growth plates are abnormally calcified

• however, bone volume, trabecular and cortical bone mass, osteoblast and osteoclast counts, and bone formation are normal at 5 weeks of age

Genotype
MGI:3588990

cx4

• 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

cx5

• 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

cx6

• 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 )