Mouse Genome Informatics
hm
    Mgptm1Kry/Mgptm1Kry
involves: 129S7/SvEvBrd * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
mortality/aging
• homozygotes develop to term but die by 2 months of age from rupture and subsequent hemorrhage of the thoracic and abdominal aorta

cardiovascular system
• 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
• 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
• in affected aortae, smooth muscle cells fail to retain their spatial arrangement as discrete, contiguous layers throughout the vessel wall
• at 2 and 3 weeks of age, homozygotes show widespread calcification along the aorta and its branches; 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
• notably, calcification occurs in the absence of fatty streak or atherosclerotic plaques
• 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
• total capillary density and the number of capillaries with a diameter of more than 20 um is increased in glomeruli
• 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
• 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
• mutants exhibit pulmonary arteriovenous malformations and shunts
• at 2 and 3 weeks of age, homozygotes exhibit calcification in coronary arteries and aortic valves but not in the myocardium
• homozygotes die from rupture and subsequent hemorrhage of the thoracic and abdominal aorta
• beginning at 2 weeks of age, homozygotes display a significantly faster heart rate than wild-type mice

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

skeleton
• homozygotes display inappropriate calcification of cartilage in the lower end of the trachea
• at 8 weeks, homozygotes display inappropriate calcification of the growth-plate cartilage
• 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
• abnormal calcification of the growth plate cartilage results in the absence of hypertrophic chondorcytes
• abnormal calcification of the growth-plate cartilage leads to osteopenia and fractures

respiratory system
• mutants exhibit a paucity of terminal airways
• 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
• lungs are slightly smaller
• homozygotes display inappropriate calcification of cartilage in the main bronchi
• homozygotes display inappropriate calcification of cartilage in the lower end of the trachea

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

renal/urinary system
• 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
• kidneys show more glomeruli per microscopic field than controls
• mutants exhibit abnormal arteriovenous connections in the glomeruli
• total capillary density and the number of capillaries with a diameter of more than 20 um is increased in glomeruli
• kidneys are heavier when normalized to total body weight
• kidneys are slightly smaller

Mouse Models of Human Disease
OMIM IDRef(s)
Singleton-Merten Syndrome 182250 J:38867