Phenotypes Associated with This Genotype

Genotype
MGI:2657020

• Allelic Composition: Lox^tm1Ikh/Lox^tm1Ikh
• Genetic Background: involves: 129X1/SvJ * C57BL/6J

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

Thoracic aorta abnormalities in Lox^tm1Ikh/Lox^tm1Ikh mice

skeleton

abnormal diaphragm central tendon morphology ( J:82926 )

• homozygotes display compromised tensile strength in the collagen-rich central tendon of the diaphragm; only fragments of the central tendon are observed

mortality/aging

perinatal lethality, complete penetrance ( J:82926 )

• homozygotes die shortly after delivery following birth trauma, cardiovascular events, and/or diaphragmatic rupture

cardiovascular system

abnormal aorta wall morphology ( J:82926 )

• discontinuity of collagen in the aortic lamellae and impaired continuity of smooth muscle cells is observed

• aortic rupture occurs predominantly in the perinatal period

abnormal aorta smooth muscle morphology ( J:82926 )

• the mutant descending thoracic aorta displays impaired continuity of smooth muscle cells

decreased aorta wall thickness ( J:82926 )

• aorta wall thickness is variable and often significantly reduced

abnormal descending thoracic aorta morphology ( J:82926 )

• the mutant descending thoracic aorta is always significantly tortuous with maximal displacement to the right and left, denoting aortic lengthening

aortic aneurysm ( J:82926 )

• soon after parturition, homozygotes display ruptured aortic aneurysms

abnormal blood vessel elastic tissue morphology ( J:82926 )

• newborn homozygotes exhibit a fragmented, disordered elastic fiber architecture around pulmonary vessels and conducting airways and in thoracic aortae

abnormal aorta elastic tissue morphology ( J:82926 )

• as early as E14.5, homozygotes display progressive fragmentation and discontinuity of the internal elastic lamina with fragmented, aberrant lamellae

decreased aorta elastin content ( J:82926 )

• homozygotes exhibit a ~60% reduction of elastin cross-links in the aorta and lungs; immature collagen cross-links are also reduced albeit to a lesser extent (~40%)

hemothorax ( J:82926 )

• most homozygotes display hemothorax

hemoperitoneum ( J:82926 )

• most homozygotes display hemoperitoneum

respiratory system

hemothorax ( J:82926 )

• most homozygotes display hemothorax

muscle

abnormal aorta smooth muscle morphology ( J:82926 )

• the mutant descending thoracic aorta displays impaired continuity of smooth muscle cells

abnormal diaphragm development ( J:82926 )

• homozygotes often exhibit either unilateral or bilateral diaphragmatic rupture

• rupture occasionally occurs during the last days of gestation but most frequently at birth upon breathing initiation

abnormal diaphragm central tendon morphology ( J:82926 )

• homozygotes display compromised tensile strength in the collagen-rich central tendon of the diaphragm; only fragments of the central tendon are observed

diaphragmatic hernia ( J:82926 )

• diaphragmatic rupture results in herniation of abdominal contents into the thorax; the liver and stomach displace the heart from the mid-chest and compress the lungs

integument

decreased skin tensile strength ( J:82926 )

• upon dissection, mutant skin tears easily

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Menkes disease		DOID:1838	OMIM:309400	J:82926