Phenotypes associated with this allele

• Allele Symbol: Invs^inv
• Allele Name: inversion of embryonic turning
• Allele ID: MGI:1856915
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Invs^inv/Invs^inv	FVB/N-Invs^inv	MGI:3622553
hm2	Invs^inv/Invs^inv	involves: C57BL/6 * FVB/N	MGI:4889195
hm3	Invs^inv/Invs^inv	involves: FVB/N	MGI:2654613
ht4	Invs^inv/Invs^+	FVB/N-Invs^inv	MGI:3622556
cx5	Foxj1^tm1Bph/Foxj1^tm1Bph Invs^inv/Invs^inv	involves: C57BL/6 * FVB/N	MGI:4889194

Genotype
MGI:3622553

hm1

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

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

growth/size/body

atrial situs inversus ( J:48533 )

• 85% exhibit atrial situs inversus, 7.5% with incomplete inversus, and 7.5% with left isomerism

right-sided stomach ( J:48533 )

• all have right-sided stomach, however the angle between the cardia and the pylorus of the stomach varies

abdominal situs ambiguus ( J:48533 )

• 20% exhibit abdominal heterotaxy, with an abdomen characterized by a symmetrical liver, hypoplastic spleen, small-lobed pancreas, and malrotation of the common gastrointestinal mesentery

left-sided isomerism ( J:48533 )

left atrial isomerism ( J:48533 )

• 7.5% exhibit left atrial isomerism

left pulmonary isomerism ( J:48533 )

• 4 of 40 exhibit left isomerism of the lung, in which both sides of the lung are unilobed or pseudobilobed, and associated with hyparterial bronchi

lung situs inversus ( J:48533 )

• 40% exhibit situs inversus of the lung and 50% show incomplete inversus

situs ambiguus ( J:48533 )

• 25% show visceroatrial heterotaxy

situs inversus ( J:48533 )

• each organ shows primary situs inversus with variable degrees of irregularity, ranging from almost complete form of situs inversus to left isomerism

cardiovascular system

abnormal vena cava morphology ( J:48533 )

• mutants sometimes exhibit posterior vena cava interruption

abnormal heart morphology ( J:48533 )

• mutants exhibit cardiovascular anomalies that are seen in various combinations

• 10% exhibit tetralogy of Fallot; seen in 20% of mutants with abdominal heterotaxy and 25% of mutants with visceroatrial heterotaxy

abnormal atrioventricular cushion morphology ( J:48533 )

• mutants sometimes have an endocardial cushion defect

double outlet right ventricle ( J:48533 )

• seen occasionally

transposition of great arteries ( J:48533 )

• seen occasionally

atrial situs inversus ( J:48533 )

• 85% exhibit atrial situs inversus, 7.5% with incomplete inversus, and 7.5% with left isomerism

left atrial isomerism ( J:48533 )

• 7.5% exhibit left atrial isomerism

dextrocardia ( J:48533 )

aortic valve stenosis ( J:48533 )

• mutants sometimes display aortic stenosis

digestive/alimentary system

right-sided stomach ( J:48533 )

• all have right-sided stomach, however the angle between the cardia and the pylorus of the stomach varies

abnormal intestine morphology ( J:48533 )

• 42.5% show incompletely inverted looping of the intestine, 35% show malrotation, and 20% almost complete inversion of the intestinal loop

hematopoietic system

abnormal spleen morphology ( J:48533 )

• 55% have normal sized spleen which is located along the great curvature of the right-sided stomach and 9% show a dysplastic spleen which is located bilaterally across the central line of the abdomen

spleen hypoplasia ( J:48533 )

• 22% have a hypoplastic spleen

liver/biliary system

abnormal liver morphology ( J:48533 )

• 35% show situs inversus of the liver, 20% have primary situs inversus with incomplete lobation, and 45% have left isomerism of the liver, in which the hepatic portion of the posterior vena cava is absent

respiratory system

left pulmonary isomerism ( J:48533 )

• 4 of 40 exhibit left isomerism of the lung, in which both sides of the lung are unilobed or pseudobilobed, and associated with hyparterial bronchi

lung situs inversus ( J:48533 )

• 40% exhibit situs inversus of the lung and 50% show incomplete inversus

endocrine/exocrine glands

abnormal pancreas morphology ( J:48533 )

• 68% have a warped pancreas which runs along the duodenal looping, but is almost normal in size, and the rest have severe hypoplasia of the pancreas

immune system

abnormal spleen morphology ( J:48533 )

• 55% have normal sized spleen which is located along the great curvature of the right-sided stomach and 9% show a dysplastic spleen which is located bilaterally across the central line of the abdomen

spleen hypoplasia ( J:48533 )

• 22% have a hypoplastic spleen

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
tetralogy of Fallot		DOID:6419	OMIM:187500	J:48533

Genotype
MGI:4889195

hm2

• Allelic Composition: Invs^inv/Invs^inv
• Genetic Background: involves: C57BL/6 * FVB/N

cardiovascular system

right aortic arch ( J:104135 )

• at E18.5, most homozygotes (11 of 16) display a right-sided aortic arch

double aortic arch ( J:104135 )

• at E18.5, 1 of 16 homozygotes displays a double aortic arch

aorta hypoplasia ( J:104135 )

• at E18.5, 1 of 16 homozygotes displays a right-sided aortic arch with an underdeveloped aorta

dextrocardia ( J:104135 )

• at E18.5, the heart is malpositioned to the right

respiratory system

left pulmonary isomerism ( J:104135 )

• at E18.5, 1 of 16 homozygotes displays left pulmonary isomerism

lung situs inversus ( J:104135 )

• at E18.5, >50% of homozygotes display a reversal of lung laterality resulting in a single-lobed right lung and a four-lobed left lung

right pulmonary isomerism ( J:104135 )

• at E18.5, 3 of 16 homozygotes display right pulmonary isomerism

digestive/alimentary system

right-sided stomach ( J:104135 )

• at E18.5, 10 of 16 homozygotes display a right-sided stomach

• the sidedness of the aortic arch and stomach is concordant

growth/size/body

right-sided stomach ( J:104135 )

• at E18.5, 10 of 16 homozygotes display a right-sided stomach

• the sidedness of the aortic arch and stomach is concordant

left pulmonary isomerism ( J:104135 )

• at E18.5, 1 of 16 homozygotes displays left pulmonary isomerism

lung situs inversus ( J:104135 )

• at E18.5, >50% of homozygotes display a reversal of lung laterality resulting in a single-lobed right lung and a four-lobed left lung

right pulmonary isomerism ( J:104135 )

• at E18.5, 3 of 16 homozygotes display right pulmonary isomerism

Genotype
MGI:2654613

hm3

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

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)

• cysts first appear in collecting ducts and proximal tubules by E17 (J:132552)

• 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 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 )

• 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

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

Genotype
MGI:3622556

ht4

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

liver/biliary system

abnormal liver morphology ( J:48533 )

• often exhibit deformation of the inner left lobe of the liver, however display no cardiovascular abnormalities

Genotype
MGI:4889194

cx5

• Allelic Composition: Foxj1^tm1Bph/Foxj1^tm1Bph; Invs^inv/Invs^inv
• Genetic Background: involves: C57BL/6 * FVB/N

respiratory system

right pulmonary isomerism ( J:104135 )

• at E18.5, nearly all (18 of 21) double homozygotes display right pulmonary isomerism

• right pulmonary isomerism is likely due to absence of Pitx2 expression in both lateral plate mesoderms at E8.5

cardiovascular system

right aortic arch ( J:104135 )

• at E18.5, 10 of 21 double homozygotes display a right-sided aortic arch

• the remaining 11 show a normal left-sided aortic arch

aorta hypoplasia ( J:104135 )

• at E18.5, 3 of the 11 double homozygotes with a normal left-sided aortic arch display an underdeveloped aorta

digestive/alimentary system

right-sided stomach ( J:104135 )

• at E18.5, 61% of double homozygotes display a right-sided stomach

• no colinearity of the sidedness between the aortic arch and stomach is observed

growth/size/body

right-sided stomach ( J:104135 )

• at E18.5, 61% of double homozygotes display a right-sided stomach

• no colinearity of the sidedness between the aortic arch and stomach is observed

right pulmonary isomerism ( J:104135 )

• at E18.5, nearly all (18 of 21) double homozygotes display right pulmonary isomerism

• right pulmonary isomerism is likely due to absence of Pitx2 expression in both lateral plate mesoderms at E8.5