Mouse Genome Informatics
hm
    Invsinv/Invsinv
involves: FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
mortality/aging
• do not survive beyond 7 days of age (J:4934)
• usually die within the first week of life; one pup survived to P11 (J:132552)

cardiovascular system
• 6 of 8 have an inverted cardiac l-loop and the direction of looping is ambiguous in the other two

embryogenesis
• although embryonic nodal cilia rotate as rapidly as those of wild-type embryos, the nodal flow is less smooth, much slower than normal, and more turbulent resulting in a slow net leftward transport in the node
• development of nodal flow arrests at nodal stage 3 or 4 and does not proceed to nodal stage 5
• direction of embryonic turning is reversed as the vitalline vessels are situated on the right size of the body
• aberrant cell masses are found around the node, which often deform the node shape and alter the positional arrangement of nodal cilia
• the positional arrangement of nodal cilia is often altered

growth/size
• do not increase in size after birth (J:4934)
• do not increase in weight after birth
• poor weight gain after P2
• 100% exhibit situs inversus, with stomach, spleen, heart, lungs, and liver being mirror-image left-right inversions (J:4934)
• spleen and the apex of the heart found on the right side instead of the left (J:132552)

liver/biliary system
• biliary obstruction or atresia
• yellow discoloration of skin (J:132552)

renal/urinary system
N
• in culture, primary mutant renal epithelial cells show no significant differences in the % of ciliated cells or in primary cilia length relative to wild-type controls (J:112771)
• primary mutant renal cilia exhibit normal bending mechanics in response to physiological fluid flow relative to wild-type cilia (J:112771)
• mutant proximal renal epithelial cells show a normal rise in intracellular Ca2+ concentration in response to fluid flow stress relative to wild-type cells (J:112771)
• normal-looking primary cilia (monocilia) are seen at apical surfaces of cystic collecting ducts and proximal tubules at P5 (J:132552)
• significant kidney pathology with dilated tubules and abnormal glomeruli
• within a couple of days after birth, kidneys are filled with severely dilated collecting ducts (J:49759)
• fusiform dilatation of collecting ducts at P5 (J:132552)
• cystic collecting ducts are uniformly and diffusely dilated throughout their entire lengths, except at the most proximal tips in the superficial cortex (J:132552)
• collecting ducts may appear haphazardly arranged in 2-D; however, 3-D imaging indicates that they maintain their parallel alignment from medulla to cortex (J:132552)
• expansion of Bowman's space surrounding deep cortical glomeruli is first noted at E15 and persists through P11
• relatively disorganized and more abundant interstitium at P5
• defects in the organization of the pelvic region
• at P7, cystic kidneys weigh more than twice as much as wild-type kidneys
• thin descending loops of Henle are narrowed at their transitions from S3 segments
• some of these thin loops have diverticuli or flaring at their distal ends
• focal thinning of the apical brush border microvilli within progressively expanding cysts
• at P5, rarified microvilli resemble loose, ill-fitting pieces of jigsaw puzzles
• soon after birth, tubules are severely dilated (J:50117)
• fusiform (not secular) dilatation of convoluted and straight proximal tubules, bridged by segments of normal or narrowed calibers at P3 and P5 (J:132552)
• variable luminal widening and cyst formation at P5
• fusiform cysts, hairpin turns and narrowed segments in a single P4 convoluted proximal tubule
• rare, small outpocketings seen along proximal tubules
• variously sized tubular cysts (J:81042)
• relatively rapid development and progression of epithelial-lined renal cysts (J:132552)
• expansion of Bowman's space surrounding deep cortical glomeruli already noted at E15 (J:132552)
• cysts first appear in collecting ducts and proximal tubules by E17 (J:132552)
• cysts of increased size and number involving collecting ducts, proximal tubules and Bowman's spaces at P1 (J:132552)
• more extensive, diffuse cortical and medullary cysts at P11 (J:132552)
• diffuse and elaborate cortical cysts noted at P11, more extensive than at P1
• diffuse and elaborate medullary cysts noted at P11, more extensive than at P1
• corticomedullary cysts involving collecting ducts, proximal tubules, and thick ascending limbs at P5
• cystic dilatation of some glomeruli
• dystrophic calcifications in less than 5% of tubular lumina by P11
• succumb to renal failure within 1 wk of life

digestive/alimentary system
• dilation of many of the acinar ducts
• vacuolization of the pancreatic acinar cells
• decrease in the number of exocrine acinar cells
• dilation of the pancreatic ducts

endocrine/exocrine glands
• dilation of many of the acinar ducts
• vacuolization of the pancreatic acinar cells
• decrease in the number of exocrine acinar cells
• dilation of the pancreatic ducts
• expansion and disorganization of the endocrine cells in the islets of Langerhans

homeostasis/metabolism
• 2-fold increase in blood urea nitrogen levels by P5

respiratory system
N
• normal 9 + 2 arrangement seen in respiratory cilia from trachea at P5 (J:132552)

cellular
• the positional arrangement of nodal cilia is often altered
• although embryonic nodal cilia rotate as rapidly as those of wild-type embryos, the nodal flow is less smooth, much slower than normal, and more turbulent resulting in a slow net leftward transport in the node
• development of nodal flow arrests at nodal stage 3 or 4 and does not proceed to nodal stage 5

Mouse Models of Human Disease
OMIM IDRef(s)
Nephronophthisis 2; NPHP2 602088 J:132552