Phenotypes Associated with This Genotype

Genotype
MGI:2654613

• Allelic Composition: Invs^inv/Invs^inv
• Genetic Background: involves: FVB/N

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

mortality/aging

postnatal lethality ( J:4934 , J:50117 , J:132552 )

• 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

abnormal direction of heart looping ( J:4934 )

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

embryo

abnormal motile primary cilium physiology ( J:109561 )

• 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

abnormal direction of embryo turning ( J:4934 )

• direction of embryonic turning is reversed as the vitalline vessels are situated on the right size of the body

abnormal primitive node morphology ( J:109561 )

• aberrant cell masses are found around the node, which often deform the node shape and alter the positional arrangement of nodal cilia

abnormal embryonic cilium location or orientation ( J:109561 )

• the positional arrangement of nodal cilia is often altered

growth/size/body

kidney cyst ( J:49759 , J:81042 , J:132552 )

• 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)

kidney cortex cyst ( J:132552 )

• diffuse and elaborate cortical cysts noted at P11, more extensive than at P1

kidney corticomedullary cyst ( J:132552 )

• corticomedullary cysts involving collecting ducts, proximal tubules, and thick ascending limbs at P5

kidney medulla cyst ( J:132552 )

• diffuse and elaborate medullary cysts noted at P11, more extensive than at P1

renal glomerulus cyst ( J:81042 )

• cystic dilatation of some glomeruli

decreased body size ( J:4934 , J:132552 )

• do not increase in size after birth (J:4934)

decreased body weight ( J:4934 )

• do not increase in weight after birth

slow postnatal weight gain ( J:132552 )

• poor weight gain after P2

situs inversus ( J:4934 , J:49759 , J:50117 , J:132552 )

• 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)

increased kidney weight ( J:132552 )

• at P7, cystic kidneys weigh more than twice as much as wild-type kidneys

liver/biliary system

abnormal biliary tract morphology ( J:50117 )

• biliary obstruction or atresia

jaundice ( J:4934 , J:50117 , J:132552 )

• yellow discoloration of skin (J:132552)

renal/urinary system

renal/urinary system phenotype ( J:112771 , J:132552 )

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)

N • primary mutant renal cilia exhibit normal bending mechanics in response to physiological fluid flow relative to wild-type cilia (J:112771)

N • 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)

N • normal-looking primary cilia (monocilia) are seen at apical surfaces of cystic collecting ducts and proximal tubules at P5 (J:132552)

abnormal kidney morphology ( J:4934 )

• significant kidney pathology with dilated tubules and abnormal glomeruli

kidney cyst ( J:49759 , J:81042 , J:132552 )

• 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)

kidney cortex cyst ( J:132552 )

• diffuse and elaborate cortical cysts noted at P11, more extensive than at P1

kidney corticomedullary cyst ( J:132552 )

• corticomedullary cysts involving collecting ducts, proximal tubules, and thick ascending limbs at P5

kidney medulla cyst ( J:132552 )

• diffuse and elaborate medullary cysts noted at P11, more extensive than at P1

renal glomerulus cyst ( J:81042 )

• cystic dilatation of some glomeruli

increased kidney weight ( J:132552 )

• at P7, cystic kidneys weigh more than twice as much as wild-type kidneys

dilated kidney collecting duct ( J:49759 , J:50117 , J:132552 )

• 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)

increased glomerular capsule space ( J:132552 )

• expansion of Bowman's space surrounding deep cortical glomeruli is first noted at E15 and persists through P11

abnormal renal glomerulus morphology ( J:4934 )

abnormal kidney interstitium morphology ( J:132552 )

• relatively disorganized and more abundant interstitium at P5

abnormal kidney pelvis morphology ( J:50117 )

• defects in the organization of the pelvic region

abnormal loop of Henle ascending limb thick segment morphology ( J:132552 )

• thick ascending limbs appear dilated

abnormal loop of Henle descending limb morphology ( J:132552 )

• some of these thin loops have diverticuli or flaring at their distal ends

• thin descending loops of Henle are narrowed at their transitions from S3 segments

proximal convoluted tubule brush border loss ( J:132552 )

• focal thinning of the apical brush border microvilli within progressively expanding cysts

• at P5, rarified microvilli resemble loose, ill-fitting pieces of jigsaw puzzles

dilated renal tubule ( J:4934 , J:50117 , J:132552 )

• 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)

dilated proximal convoluted tubule ( 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

nephrocalcinosis ( J:132552 )

• dystrophic calcifications in less than 5% of tubular lumina by P11

kidney failure ( J:132552 )

• succumb to renal failure within 1 wk of life

digestive/alimentary system

abnormal pancreatic acinus morphology ( J:50117 )

• dilation of many of the acinar ducts

abnormal pancreatic acinar cell morphology ( J:50117 )

• vacuolization of the pancreatic acinar cells

decreased pancreatic acinar cell number ( J:50117 )

• decrease in the number of exocrine acinar cells

dilated pancreatic duct ( J:50117 )

• dilation of the pancreatic ducts

endocrine/exocrine glands

abnormal pancreatic acinus morphology ( J:50117 )

• dilation of many of the acinar ducts

abnormal pancreatic acinar cell morphology ( J:50117 )

• vacuolization of the pancreatic acinar cells

decreased pancreatic acinar cell number ( J:50117 )

• decrease in the number of exocrine acinar cells

dilated pancreatic duct ( J:50117 )

• dilation of the pancreatic ducts

abnormal pancreatic islet morphology ( J:50117 )

• expansion and disorganization of the endocrine cells in the islets of Langerhans

pancreatic islet hyperplasia ( J:50117 )

disorganized pancreatic islets ( J:50117 )

homeostasis/metabolism

increased blood urea nitrogen level ( J:132552 )

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

respiratory system

respiratory system phenotype ( J:132552 )

N • normal 9 + 2 arrangement seen in respiratory cilia from trachea at P5

cellular

abnormal embryonic cilium location or orientation ( J:109561 )

• the positional arrangement of nodal cilia is often altered

abnormal motile primary cilium physiology ( J:109561 )

• 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		DO ID	OMIM ID(s)	Ref(s)
nephronophthisis 2		DOID:0111113	OMIM:602088	J:132552