mortality/aging
• mice are born at the expected ratio but most die within the first two days after birth
(J:38838)
• some survival to several weeks or several months of age does occur
(J:38838)
|
renal/urinary system
• at E13.5, 54% of mutants exhibit degenerating metanephric mesenchyme
(J:38838)
• in 18% of mutants at E13.5, ureter branching and epithelial specialization is seen but always at a reduced level compared to controls
(J:38838)
• in about 14% of mutants born the ureter fails to branch in the metanephric mesenchyme and no nephrons form
(J:38838)
• in 26% of mutants born, ureter branching is more extensive and excretory nephrons are present
(J:38838)
• kidney rudiments are poorly organized and only 17% of mice showed epithelial specialization at birth
(J:38838)
• at E11.5, all mutants display lack of invasion of metanephtric mesenchyme by ureteric bud
(J:122519)
|
small kidney
(
J:38838
)
• when surviving mutants interbreed, about 67% of offspring survived and had 1-2 small kidneys
|
• in about 54% of mutants
(J:38838)
• 59% kidney agenesis incidence
(J:122519)
|
single kidney
(
J:38838
)
• all mice that survive more than a few days have a single kidney
|
• 40% of mutants exhibit a unilateral ureter which invades the metanephric mesenchyme but did not branch
|
absent ureter
(
J:38838
)
• in about 54% of mutants or very short
|
• at E13.5 28% of mutants show ureter invasion of metanephros but no branching or epithelial specializations
|
• at E11.5 ureteric bud formed but has not invaded metanephric mesenchyme
|
hearing/vestibular/ear
• utricular hair cells may lack stereocilia
• formation of utricular hair cells is normal but numbers with mature stereocilia declines during development
|
• utricular hair cells may contain small apical projections that resemble collapsed or fused stereocilia
|
behavior/neurological
• surviving adults often have balancing difficulty
|
nervous system
• utricular hair cells may lack stereocilia
• formation of utricular hair cells is normal but numbers with mature stereocilia declines during development
|
• utricular hair cells may contain small apical projections that resemble collapsed or fused stereocilia
|
respiratory system
• at E18 or later, mutant lungs display defective saccular airway branching and division
|
• at E18 or later, mutant saccular airways are irregular in size and shape and appear more dilated than in wild-type lungs
• dilated saccular airways lead to an increased distal luminal airway volume
• saccular airway division and septal height are reduced in neonatal lungs
• after 72 hrs of culture, E16 (saccular stage) fetal lung explants exhibit more dilated saccular airways with fewer divisions and reduced elongation
|
• although all 5 lobes (4 right, 1 left) form normally present at E13, 90% of homozygotes display fusion of the medial and caudal lobes of the right lung at E16
• after 48 hrs of culture on nylon filters, cranial and accessory lobes from E15 mutant mice grow together forming multiple cellular bridges between adjacent lobes, unlike wild-type lobes which remain separate with no signs of attachment
• lung lobe fusion is attributed to defects in cell-matrix interactions and increased cell migration of mesenchymal cells
• lobe fusion is not due to lack of mesothelium formation, as flattened, elongated mesothelial cells are normally present along the lung periphery
|
• 90% of homozygotes display fusion of the medial and caudal lobes of the right lung at E16
|
• irregular, dilated airspaces found adjacent to areas with small or collapsed airways
|
• neonatal lungs display abnormally wavy and short elastic fibers
• however, the total amount of elastin is not significantly altered
|
• neonatal lungs display irregular, dilated airspaces adjacent to areas with small or collapsed airways
• airway diameter, as measured by mean linear intercept, is increased
|
cellular
• when plated onto fibronectin, mutant fetal (E16) lung mesenchymal cells develop fewer focal contacts and less transcellular stress fibers than wild-type mesenchymal cells
|
• in fetal (E16) lung explant cultures, mutant mesenchymal cells display both random and increased cell migration around newly formed saccular airways relative to wild-type mesenchymal cells
|