Phenotypes associated with this allele

• Allele Symbol: Pax8⁺
• Allele Name: wild type
• Allele ID: MGI:2431554
• Summary: 11 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
ht1	Pax8^tm1Rdl/Pax8^+	B6.129-Pax8^tm1Rdl	MGI:5775547
ht2	Pax8^tm1Pgr/Pax8^+	either: (involves: 129S1/Sv * 129X1/SvJ) or (involves: 129S1/Sv * 129X1/SvJ * C57BL/6)	MGI:3694005
cn3	Dicer1^tm1Smr/Dicer1^tm1Smr Pax8^tm1.1(cre)Mbu/Pax8^+	involves: 129P2/OlaHsd * 129S7/SvEvBrd	MGI:5792829
cn4	Gal3st1^tm1.1Hjg/Gal3st1^tm1.1Hjg Ugcg^tm1Hjg/Ugcg^tm1Hjg Pax8^tm1.1(cre)Mbu/Pax8^+	involves: 129P2/OlaHsd * C57BL/6	MGI:5521180
cn5	Gal3st1^tm1.1Hjg/Gal3st1^tm1.1Hjg Pax8^tm1.1(cre)Mbu/Pax8^+	involves: 129P2/OlaHsd * C57BL/6	MGI:5521179
cn6	Pax8^tm1.1(cre)Mbu/Pax8^+ Plxnb2^tm1.1Rkun/Plxnb2^tm1.1Rkun	involves: 129P2/OlaHsd * C57BL/6	MGI:5807121
cn7	Pax8^tm1.1(cre)Mbu/Pax8^+ Plxnb1^tm1Rkun/Plxnb1^tm1Rkun Plxnb2^tm1.1Rkun/Plxnb2^tm1.1Rkun	involves: 129P2/OlaHsd * C57BL/6	MGI:5807122
cn8	Hnrnpf^tm1Jsdc/Hnrnpf^tm1Jsdc Pax8^tm1.1(cre)Mbu/Pax8^+	involves: 129P2/OlaHsd * C57BL/6	MGI:6392034
cn9	Ugcg^tm1Hjg/Ugcg^tm1Hjg Pax8^tm1.1(cre)Mbu/Pax8^+	involves: 129P2/OlaHsd * C57BL/6	MGI:5521181
cn10	Dkk1^tm1.1Svo/Dkk1^tm1.2Svo Pax8^tm1.1(cre)Mbu/Pax8^+	involves: 129P2/OlaHsd * C57BL/6 * SJL	MGI:5013426
cx11	Pax2^tm1Mbu/Pax2^+ Pax8^tm1(cre)Mbu/Pax8^+	involves: 129P2/OlaHsd * C3H/He * C57BL/6	MGI:2651548

Genotype
MGI:5775547

ht1

• Allelic Composition: Pax8^tm1Rdl/Pax8⁺
• Genetic Background: B6.129-Pax8^tm1Rdl

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

normal phenotype

no abnormal phenotype detected ( J:220108 )

• mice are viable, healthy and born at the expected Mendelian ratio

Genotype
MGI:3694005

ht2

• Allelic Composition: Pax8^tm1Pgr/Pax8⁺
• Genetic Background: either: (involves: 129S1/Sv * 129X1/SvJ) or (involves: 129S1/Sv * 129X1/SvJ * C57BL/6)

homeostasis/metabolism

increased circulating thyroid-stimulating hormone level ( J:47310 )

• surprisingly, heterozygotes do not display an obvious thyroid phenotype

• serum TSH levels are more frequently elevated in heterozygous relative to wild-type mice

Genotype
MGI:5792829

cn3

• Allelic Composition: Dicer1^tm1Smr/Dicer1^tm1Smr; Pax8^{tm1.1(cre)Mbu}/Pax8⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S7/SvEvBrd

renal/urinary system

increased kidney apoptosis ( J:229188 )

• apoptosis is frequently seen in shedding cells in both the Bowman space and in the lumen of the tubules, occurring more frequently at P50

increased kidney cell proliferation ( J:229188 )

• the tubular epithelium and parietal cells of the renal corpuscles show increased cellular proliferation in the phase of cyst growth

decreased urine osmolality ( J:229188 )

• at P30, urinary osmolality is lower, with no changes in urinary ouput or in collecting duct distribution

increased urine protein level ( J:229188 )

• mice develop progressively massive proteinuria, consisting mainly of albuminuria that is already higher at P30

albuminuria ( J:229188 )

• seen by P30

abnormal kidney morphology ( J:229188 )

• kidneys at P50 have a rough surface

abnormal renal tubule epithelial cell primary cilium morphology ( J:229188 )

• at P50, primary cilia are rare in the epithelium of dilating tubules and absent in enlarged cysts with flattened epithelium, indicating a progressive loss of primary cilia with cyst enlargement

kidney cortex cyst ( J:229188 )

• at P50, mice exhibit cortical cysts

• cysts originate from the renal corpuscles of the cortex and are absent in the outer and inner medulla

decreased kidney collecting duct number ( J:229188 )

• the density of collecting ducts is lower at P50

abnormal renal corpuscle morphology ( J:229188 )

• the tubular epithelium and parietal cells of the renal corpuscles show increased cellular proliferation in the phase of cyst growth, before flattening of the cystic epithelium

dilated renal glomerular capsule ( J:229188 )

• dilatation of the parietal cells of the Bowman capsule

abnormal renal glomerulus morphology ( J:229188 )

• glomeruli progressively shrink

• mice develop glomerulocystic disease

renal interstitial fibrosis ( J:229188 )

• epithelium lining the cyst flattens and interstitial fibrosis develops

decreased kidney weight ( J:229188 )

• mice present lower kidney weight at P50, with the ratio of kidney weight/body weight being lower at P50 but not P30

dilated renal tubule ( J:229188 )

• tubular dilatations are mainly cortical and develop progressively at P50

pale kidney ( J:229188 )

• kidneys at P50 have a paler color

decreased renal glomerular filtration rate ( J:229188 )

isosthenuria ( J:229188 )

• progressive impairment of urinary concentrating ability

polyuria ( J:229188 )

• increase in urine output at P50 but not P30

cellular

abnormal renal tubule epithelial cell primary cilium morphology ( J:229188 )

• at P50, primary cilia are rare in the epithelium of dilating tubules and absent in enlarged cysts with flattened epithelium, indicating a progressive loss of primary cilia with cyst enlargement

increased kidney apoptosis ( J:229188 )

• apoptosis is frequently seen in shedding cells in both the Bowman space and in the lumen of the tubules, occurring more frequently at P50

increased kidney cell proliferation ( J:229188 )

• the tubular epithelium and parietal cells of the renal corpuscles show increased cellular proliferation in the phase of cyst growth

growth/size/body

decreased body weight ( J:229188 )

• mice present lower body weight at P30

kidney cortex cyst ( J:229188 )

• at P50, mice exhibit cortical cysts

• cysts originate from the renal corpuscles of the cortex and are absent in the outer and inner medulla

homeostasis/metabolism

decreased urine osmolality ( J:229188 )

• at P30, urinary osmolality is lower, with no changes in urinary ouput or in collecting duct distribution

increased urine protein level ( J:229188 )

• mice develop progressively massive proteinuria, consisting mainly of albuminuria that is already higher at P30

albuminuria ( J:229188 )

• seen by P30

behavior/neurological

increased fluid intake ( J:229188 )

• increase in water intake at P30 and P50

Genotype
MGI:5521180

cn4

• Allelic Composition: Gal3st1^tm1.1Hjg/Gal3st1^tm1.1Hjg; Ugcg^tm1Hjg/Ugcg^tm1Hjg; Pax8^{tm1.1(cre)Mbu}/Pax8⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

mortality/aging

mortality/aging ( J:197393 )

N • normal life span

renal/urinary system

renal/urinary system phenotype ( J:197393 )

N • normal kidney morphology and creatinine clearance

abnormal urine homeostasis ( J:197393 )

decreased urine ammonia level ( J:197393 )

• decreased ammonium excretion

• reduced ability to increase urinary ammonia

increased urine potassium level ( J:197393 )

decreased urine pH ( J:197393 )

• higher excretion of titratable acid relative to controls

• less ability to recover from high acid in the diet

abnormal kidney papilla morphology ( J:197393 )

• ammonium content of the renal papilla is reduced 30% compared to controls

polyuria ( J:197393 )

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:197393 )

N • normal blood pH

N • normal blood bicarbonate levels

abnormal urine homeostasis ( J:197393 )

decreased urine ammonia level ( J:197393 )

• decreased ammonium excretion

• reduced ability to increase urinary ammonia

increased urine potassium level ( J:197393 )

decreased urine pH ( J:197393 )

• higher excretion of titratable acid relative to controls

• less ability to recover from high acid in the diet

Genotype
MGI:5521179

cn5

• Allelic Composition: Gal3st1^tm1.1Hjg/Gal3st1^tm1.1Hjg; Pax8^{tm1.1(cre)Mbu}/Pax8⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

mortality/aging

mortality/aging ( J:197393 )

N • normal life span

renal/urinary system

renal/urinary system phenotype ( J:197393 )

N • normal kidney morphology and creatinine clearance

abnormal urine homeostasis ( J:197393 )

decreased urine ammonia level ( J:197393 )

• decreased ammonium excretion

• reduced ability to increase urinary ammonia

increased urine potassium level ( J:197393 )

decreased urine pH ( J:197393 )

• higher excretion of titratable acid relative to controls

• less ability to recover from high acid in the diet

polyuria ( J:197393 )

homeostasis/metabolism

metabolic acidosis ( J:197393 )

• increased metabolic acidosis

abnormal urine homeostasis ( J:197393 )

decreased urine ammonia level ( J:197393 )

• decreased ammonium excretion

• reduced ability to increase urinary ammonia

increased urine potassium level ( J:197393 )

decreased urine pH ( J:197393 )

• higher excretion of titratable acid relative to controls

• less ability to recover from high acid in the diet

Genotype
MGI:5807121

cn6

• Allelic Composition: Pax8^{tm1.1(cre)Mbu}/Pax8⁺; Plxnb2^tm1.1Rkun/Plxnb2^tm1.1Rkun
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

homeostasis/metabolism

increased susceptibility to kidney reperfusion injury ( J:221423 )

• mice show no signs of recovery from induced bilateral kidney injury and become moribund 7 days after injury

• all tubules of the entire renal cortex and outer medulla show abnormal epithelial architecture after injury

renal/urinary system

increased susceptibility to kidney reperfusion injury ( J:221423 )

• mice show no signs of recovery from induced bilateral kidney injury and become moribund 7 days after injury

• all tubules of the entire renal cortex and outer medulla show abnormal epithelial architecture after injury

abnormal renal tubule epithelium morphology ( J:221423 )

• kidney histology during the acute organ damage 12 and 24 hours after ischemia/reperfusion injury is similar to wild-type mice, however 3 days after injury, renal tubular epithelial cells leave the epithelial plane and intrude into the tubular lumen which leads to a multi-layered epithelium and complete tubular occlusion by day 7

• renal tubular epithelial cells one day after injury exhibit a mitotic spindle angle that is shifted toward divisions perpendicular to the epithelial plane

• 3 days after kidney injury, a proportion of renal tubular epithelial cells fail to align their divisions with the epithelial plane

• however, kidney morphology and function are normal under basal conditions

Genotype
MGI:5807122

cn7

• Allelic Composition: Pax8^{tm1.1(cre)Mbu}/Pax8⁺; Plxnb1^tm1Rkun/Plxnb1^tm1Rkun; Plxnb2^tm1.1Rkun/Plxnb2^tm1.1Rkun
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

renal/urinary system

abnormal renal tubule epithelium morphology ( J:221423 )

• mice exhibit foci of multi-layered tubules

Genotype
MGI:6392034

cn8

• Allelic Composition: Hnrnpf^tm1Jsdc/Hnrnpf^tm1Jsdc; Pax8^{tm1.1(cre)Mbu}/Pax8⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

cardiovascular system

hypertension ( J:284239 )

• mice develop hypertension by 8 weeks of age

increased systemic arterial systolic blood pressure ( J:284239 )

• mice exhibit higher systolic blood pressure from 6 to 24 weeks of age

homeostasis/metabolism

increased angiotensin II level ( J:284239 )

• increase in urinary angiotensin II levels at 24 weeks of age

abnormal urine homeostasis ( J:284239 )

• increase in urinary angiotensin II levels at 24 weeks of age

increased urine glucose level ( J:284239 )

• increase in glucose excretion in the urine at 6 weeks of age, indicating development of glycosuria

• from 8 weeks of age, urinary glucose levels in males decrease and return to levels similar to wild-type mice at 12 weeks of age

• urinary glucose excretion in females steadily increases from week 6, reaches a plateau at 12 weeks of age and does not abate

• however, mice exhibit normal non-fasting blood glucose levels and normal glucose tolerance at 23 weeks of age

albuminuria ( J:284239 )

• increase in urinary albumin/creatinine ratio at 24 weeks of age

renal/urinary system

abnormal urine homeostasis ( J:284239 )

• increase in urinary angiotensin II levels at 24 weeks of age

increased urine glucose level ( J:284239 )

• increase in glucose excretion in the urine at 6 weeks of age, indicating development of glycosuria

• from 8 weeks of age, urinary glucose levels in males decrease and return to levels similar to wild-type mice at 12 weeks of age

• urinary glucose excretion in females steadily increases from week 6, reaches a plateau at 12 weeks of age and does not abate

• however, mice exhibit normal non-fasting blood glucose levels and normal glucose tolerance at 23 weeks of age

albuminuria ( J:284239 )

• increase in urinary albumin/creatinine ratio at 24 weeks of age

renal interstitial fibrosis ( J:284239 )

• tubule-interstitial fibrosis is seen in the kidneys at 24 weeks of age

abnormal renal tubule morphology ( J:284239 )

• increase of tubular luminal area

• however, mice show no obvious structural changes in the kidneys at 24 weeks of age, normal kidney weight/body weight ratio, normal glomerular filtration rate, and normal glomerular tuft volume

abnormal proximal convoluted tubule morphology ( J:284239 )

• increase of renal proximal tubular cell volume

polyuria ( J:284239 )

• 24 hour urine volume is increased

• however, food and water intake are normal and no differences in serum and urine levels of sodium, calcium, and phosphorus are seen

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
renal glycosuria		DOID:9432		J:284239

Genotype
MGI:5521181

cn9

• Allelic Composition: Ugcg^tm1Hjg/Ugcg^tm1Hjg; Pax8^{tm1.1(cre)Mbu}/Pax8⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

mortality/aging

mortality/aging ( J:197393 )

N • normal life span

renal/urinary system

renal/urinary system phenotype ( J:197393 )

N • normal kidney morphology and creatinine clearance

decreased urine pH ( J:197393 )

homeostasis/metabolism

decreased urine pH ( J:197393 )

Genotype
MGI:5013426

cn10

• Allelic Composition: Dkk1^tm1.1Svo/Dkk1^tm1.2Svo; Pax8^{tm1.1(cre)Mbu}/Pax8⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * SJL

renal/urinary system

increased kidney cell proliferation ( J:173125 )

• mice exhibit increased proliferation of epithelial tubules of the developing kidney papilla compared with wild-type mice

decreased urine creatinine level ( J:173125 )

decreased urine glucose level ( J:173125 )

increased urine calcium level ( J:173125 )

increased urine chloride ion level ( J:173125 )

• mice exhibit increased chloride in the urine compared with wild-type mice

decreased urine potassium level ( J:173125 )

decreased urine sodium level ( J:173125 )

decreased urine phosphate level ( J:173125 )

decreased urine protein level ( J:173125 )

abnormal kidney collecting duct epithelium morphology ( J:173125 )

• mice exhibit hypertrophic collecting duct epithelial cells at the tip of the extended renal papilla compared with wild-type mice

abnormal kidney medulla morphology ( J:173125 )

elongated kidney papilla ( J:173125 )

• mice exhibit overgrowth of renal papilla in proportion to the rest of the kidney unlike in wild-type mice

• the papilla in the medulla extends over the lateral edge of the kidney capsule and reached the epithelial lining of the lumen of the ureter outside the kidney unlike in wild-type mice

• 7 of 10 mice exhibit over extended papilla unlike in wild-type mice

hydronephrosis ( J:173125 )

• in 2 of 10 mice

oliguria ( J:173125 )

homeostasis/metabolism

decreased urine creatinine level ( J:173125 )

decreased urine glucose level ( J:173125 )

increased urine calcium level ( J:173125 )

increased urine chloride ion level ( J:173125 )

• mice exhibit increased chloride in the urine compared with wild-type mice

decreased urine potassium level ( J:173125 )

decreased urine sodium level ( J:173125 )

decreased urine phosphate level ( J:173125 )

decreased urine protein level ( J:173125 )

cellular

increased kidney cell proliferation ( J:173125 )

• mice exhibit increased proliferation of epithelial tubules of the developing kidney papilla compared with wild-type mice

Genotype
MGI:2651548

cx11

• Allelic Composition: Pax2^tm1Mbu/Pax2⁺; Pax8^tm1(cre)Mbu/Pax8⁺
• Genetic Background: involves: 129P2/OlaHsd * C3H/He * C57BL/6

renal/urinary system

decreased renal glomerulus number ( J:80208 )

• at E18.5, glomeruli are reduced in number and abnormally arranged

abnormal metanephric mesenchyme morphology ( J:80208 )

• at E18.5, the uninduced mesenchyme at the cortex and the mesenchymal stroma are increased, indicating inefficient induction of nephric tubules

small metanephros ( J:80208 )

• at E18.5, the metanephros is bilaterally reduced to only ~25% of the size in control littermates

• however, all other components of the urogenital system develop normally

renal hypoplasia ( J:80208 )

decreased nephron number ( J:80208 )

• at E18.5, nephric tubules are reduced in number and abnormally arranged

• however, remaining nephrons are functional as mice survive to >18 months of age

reproductive system

vagina atresia ( J:80208 )

♀

blind vagina ( J:80208 )

♀ • Background Sensitivity: 100% penetrance on C57BL/6 x 129/Sv background; 43% penetrance on C3H background

♀ • minor malformations are still observed in open vaginas

reduced male fertility ( J:80208 )

♂ • a significant proportion of males fail to give produce any progeny; likely due to ductal obstruction of the genital tracts rather than a defect in sperm formation