Phenotypes associated with this allele

• Allele Symbol: Pax2^1Neu
• Allele Name: Neuherberg 1
• Allele ID: MGI:1857114
• Summary: 8 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Pax2^1Neu/Pax2^1Neu	involves: 102	MGI:3841035
hm2	Pax2^1Neu/Pax2^1Neu	involves: 102 * C3H	MGI:3841029
ht3	Pax2^1Neu/Pax2^+	involves: 102	MGI:3841057
ht4	Pax2^1Neu/Pax2^+	involves: 102 * C3H	MGI:3841028
ht5	Pax2^1Neu/Pax2^+	involves: 102 * C57BL/6	MGI:3841044
ht6	Pax2^1Neu/Pax2^+	involves: 102 * CD-1	MGI:5442586
cx7	Pax2^1Neu/Pax2^+ Wt1^tm1Jae/Wt1^+	involves: 102 * 129S4/SvJae * C57BL/6	MGI:3841045
cx8	Pax2^1Neu/Pax2^+ Tg(Hoxb7-EGFP)33Cos/?	involves: 102 * C57BL/6 * CBA * CD-1	MGI:5442587

Genotype
MGI:3841035

hm1

• Allelic Composition: Pax2^1Neu/Pax2^1Neu
• Genetic Background: involves: 102

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

mortality/aging

neonatal lethality, complete penetrance ( J:89465 )

• rapid

endocrine/exocrine glands

endocrine/exocrine gland phenotype ( J:77446 )

N • unlike in zebrafish, thyroid development is normal

increased pancreatic beta cell mass ( J:89465 )

• the volume islet cells occupy in the pancreas is increased 3-fold compared to in wild-type mice

• islet cell size is increased 2.1-fold compared to in wild-type mice

increased pancreatic islet number ( J:89465 )

pancreatic islet hyperplasia ( J:89465 )

Genotype
MGI:3841029

hm2

• Allelic Composition: Pax2^1Neu/Pax2^1Neu
• Genetic Background: involves: 102 * C3H

nervous system

delayed neural tube closure ( J:37055 )

• at E6.5 in the midbrain-hindbrain region

abnormal brain development ( J:37055 )

• at E6.5, the presumptive brain region is shortened compared to in wild-type mice

absent midbrain-hindbrain boundary ( J:37055 )

• at E12.5, the midbrain-hindbrain boundary is absent

abnormal choroid plexus morphology ( J:37055 )

• the choroid plexus is fused to the superior colliculi unlike in wild-type mice

abnormal midbrain morphology ( J:37055 )

• at E14.5, the posterior mesencephalon is absent

abnormal corpora quadrigemina morphology ( J:37055 )

• the choroid plexus is fused to the superior colliculi unlike in wild-type mice

absent cerebellum ( J:37055 )

• at E14.5

abnormal vestibulocochlear ganglion morphology ( J:37055 )

• the presumptive cochlear portions of the anlagen of ganglion VIII exhibit increased apoptosis compared to in wild-type mice

exencephaly ( J:37055 )

• in some mice

abnormal optic nerve morphology ( J:37055 )

• the optic nerve contains much fewer axon fibers than in wild-type mice

hearing/vestibular/ear

abnormal inner ear morphology ( J:37055 )

• unlike in wild-type mice, an enlarged chamber is visible ventral to the semicircular canals continuing dorsally into the enlarged endolymphatic duct

abnormal inner ear development ( J:37055 )

• at E14.5, the anlagen of the cochlea is absent

absent semicircular canal ampulla ( J:37055 )

• in some mice

absent utricle ( J:37055 )

• in some mice

dilated endolymphatic duct ( J:37055 )

• enlarged

vision/eye

abnormal optic nerve morphology ( J:37055 )

• the optic nerve contains much fewer axon fibers than in wild-type mice

abnormal optic stalk morphology ( J:37055 )

• unlike in wild-type mice, the distal stalk is circular shaped

• the inner lumen of the stalk is absent and most fibers are located in the posterior wall of the stalk unlike in wild-type mice

• pigment cells are not confined to the dorsal-most regions of the stalk unlike in wild-type mice

renal/urinary system

abnormal kidney development ( J:37055 )

• at E14.5, tubules fail to form unlike in wild-type mice

abnormal metanephric mesenchyme morphology ( J:37055 )

• at E14.5, only a small anlagen of the presumptive metanephrogenic blastema is detectable unlike in wild-type mice

embryo

delayed neural tube closure ( J:37055 )

• at E6.5 in the midbrain-hindbrain region

Genotype
MGI:3841057

ht3

• Allelic Composition: Pax2^1Neu/Pax2⁺
• Genetic Background: involves: 102

endocrine/exocrine glands

increased pancreatic beta cell mass ( J:89465 )

increased pancreatic islet number ( J:89465 )

pancreatic islet hyperplasia ( J:89465 )

• the volume islet cells occupy in the pancreas is increased 2-fold compared to in wild-type mice

• islet cell size is increased 1.4-fold compared to in wild-type mice

renal/urinary system

increased kidney apoptosis ( J:136502 )

• cisplatin-exposed kidney explants exhibit a 50% increase in apoptosis compared to wild-type cells

cellular

increased kidney apoptosis ( J:136502 )

• cisplatin-exposed kidney explants exhibit a 50% increase in apoptosis compared to wild-type cells

Genotype
MGI:3841028

ht4

• Allelic Composition: Pax2^1Neu/Pax2⁺
• Genetic Background: involves: 102 * C3H

vision/eye

abnormal retina vasculature morphology ( J:37055 )

abnormal optic disk morphology ( J:37055 )

• the optic disk is abnormally broad and cup-shaped compared to in wild-type mice

abnormal retina layer morphology ( J:37055 )

• inner retinal layers are thinner than normal

abnormal retina neuronal layer morphology ( J:37055 )

• all neural layers are thinner than in wild-type mice

decreased retina ganglion cell number ( J:37055 )

thin retina ganglion layer ( J:37055 )

abnormal retina nerve fiber layer morphology ( J:37055 )

• thin

renal/urinary system

kidney cyst ( J:37055 )

• in some mice

small kidney ( J:37055 )

• in some mice

single kidney ( J:37055 )

• in 3 in 50 mice

nervous system

decreased retina ganglion cell number ( J:37055 )

abnormal optic disk morphology ( J:37055 )

• the optic disk is abnormally broad and cup-shaped compared to in wild-type mice

cardiovascular system

abnormal retina vasculature morphology ( J:37055 )

growth/size/body

kidney cyst ( J:37055 )

• in some mice

Genotype
MGI:3841044

ht5

• Allelic Composition: Pax2^1Neu/Pax2⁺
• Genetic Background: involves: 102 * C57BL/6

mortality/aging

lethality throughout fetal growth and development, incomplete penetrance ( J:86661 )

• fewer than expected mice are observed at E16

postnatal lethality, incomplete penetrance ( J:86661 )

• 23% fewer than expected mice survive beyond weaning

renal/urinary system

increased kidney apoptosis ( J:59408 , J:86661 )

• at E15-E16, a significant increase in apoptosis (as assessed by TUNEL assay) is noted in the collecting ducts and renal pelvis, as well as in the renal cortex (mostly in ureteric buds); not seen in total kidneys of E18, newborns or P1-P6 pups (J:59408)

• however, increased apoptosis is not observed in glomeruli, or proximal or distal tubules at either E15-16 or later in development (J:59408)

• also, the rate of kidney cell proliferation remains normal from E15 to P6 (J:59408)

• at E16, whole kidney apoptosis is increased compared to in wild-type mice (J:86661)

kidney cyst ( J:59408 )

• ~1% of fetuses show cystic renal abnormalities

decreased renal glomerulus number ( J:59408 , J:86661 )

• at E15-E16, the number of mature glomeruli is only 20% of that in wild-type controls (J:59408)

• compared to in wild-type mice (J:86661)

abnormal kidney development ( J:86661 )

• at E16 and E19, mice exhibit abnormal kidney development that is less severe than in Pax2^1Neu Wt1^tm1Jae heterozygotes

• however, kidney development at E13 is normal

abnormal nephrogenic zone morphology ( J:59408 )

• at E15-E16, the nephrogenic zone is thin and exhibits fewer nephrons, a primitive medulla, a reduced number of mesenchymal condensates and ureteric bud branches, and lacks mature glomeruli, unlike in wild-type controls

• the number of early epithelial structures derived from induced metanephric mesenchyme (vesicles, comma- and S-shaped bodies) is reduced to 30%-40% of wild-type controls

• however, early tubular structures and glomeruli are of normal size and morphology

kidney medulla hypoplasia ( J:59408 )

• at E15, a primitive medulla is observed, unlike the maturing medullary core seen in wild-type controls

small kidney ( J:59408 , J:86661 )

• at E15, the largest heterozygous mutant kidneys overlap in size with the smallest kidneys from wild-type controls (J:59408)

• reduced by 20% (J:86661)

renal hypoplasia ( J:59408 )

• at E15, ~60% of fetuses have hypoplastic kidneys with a maximal cross-sectional surface area ranging from 30% to 75% of that in wild-type controls

decreased nephron number ( J:59408 , J:86661 )

• at E15-E16, fewer nephrons are observed (J:59408)

• at E15, the number of early nephron structures is ~47% of that in wild-type controls (J:59408)

• kidneys contain fewer nephrons, including fewer mesenchymal condensates, comma-shaped bodies and S-shaped bodies, compared to in wild-type kidneys (J:86661)

absent kidney ( J:86661 )

• in 6% of mice

single kidney ( J:59408 )

• ~1% of fetuses show unilateral renal agenesis

impaired branching involved in ureteric bud morphogenesis ( J:59408 )

• at E15, a reduced number of ureteric bud branches is observed relative to wild-type controls

cellular

increased kidney apoptosis ( J:59408 , J:86661 )

• at E15-E16, a significant increase in apoptosis (as assessed by TUNEL assay) is noted in the collecting ducts and renal pelvis, as well as in the renal cortex (mostly in ureteric buds); not seen in total kidneys of E18, newborns or P1-P6 pups (J:59408)

• however, increased apoptosis is not observed in glomeruli, or proximal or distal tubules at either E15-16 or later in development (J:59408)

• also, the rate of kidney cell proliferation remains normal from E15 to P6 (J:59408)

• at E16, whole kidney apoptosis is increased compared to in wild-type mice (J:86661)

growth/size/body

kidney cyst ( J:59408 )

• ~1% of fetuses show cystic renal abnormalities

Genotype
MGI:5442586

ht6

• Allelic Composition: Pax2^1Neu/Pax2⁺
• Genetic Background: involves: 102 * CD-1

renal/urinary system

small kidney ( J:145105 )

• at P1, heterozygous kidneys are significantly smaller than wild-type

abnormal ureter morphology ( J:145105 )

• at E11-E17 and occasionally at P1, 27.6% of heterozygotes display hydroureters as well as bifid ureters and duplicated urinary tracts

• at P1, both left and right intravesical ureters (portion of ureter within the bladder wall) are significantly shorter than in wild-type controls

bifid ureter ( J:145105 )

• at P1, a bifid ureter with an abnormal cystic lower renal pole is sometimes observed

dilated ureter ( J:145105 )

• at P1, refluxing ureters are dilated but histologically normal

• the smooth muscle layer is intact and all ureteral layers appear grossly normal

double ureter ( J:145105 )

• duplicated ureters are sometimes observed

hydroureter ( J:145105 )

ectopic ureteric bud ( J:145105 )

• at E10.5, a more caudally positioned ureteric bud is observed relative to that in wild-type controls

• the distance from the end of the mesonephric duct to the edge of the ureteric bud is significantly shorter than in wild-type controls

• however, double ureteric buds are never seen

vesicoureteral reflux ( J:145105 )

• at P1, 31.4% of heterozygotes exhibit vesicoureteral reflux (VUR) relative to 6.25% of wild-type controls, as identified by the retrograde passage of methylene blue dye to the ureters

• both unilateral and bilateral VUR is seen; however, left-sided VUR is more frequently observed

• at P1, 45% of heterozygous males show VUR relative to only 12% of heterozygous females

• in one mouse with a duplicated urinary tract, VUR is found in both ureters extending to the upper and lower pole of the duplex kidney

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
renal coloboma syndrome		DOID:0090006	OMIM:120330	J:145105

Genotype
MGI:3841045

cx7

• Allelic Composition: Pax2^1Neu/Pax2⁺; Wt1^tm1Jae/Wt1⁺
• Genetic Background: involves: 102 * 129S4/SvJae * C57BL/6

mortality/aging

lethality throughout fetal growth and development, incomplete penetrance ( J:86661 )

• fewer than expected mice are observed at E16

postnatal lethality, incomplete penetrance ( J:86661 )

• 49% fewer than expected mice survive beyond weaning compared

renal/urinary system

increased kidney apoptosis ( J:86661 )

• at E16, whole kidney apoptosis is increased compared to in wild-type mice

abnormal kidney collecting duct morphology ( J:86661 )

• the volume of collecting ducts is reduced compared to in wild-type mice

decreased renal glomerulus number ( J:86661 )

• compared to in Pax2^1Neu heterozygotes and wild-type mice

abnormal kidney development ( J:86661 )

• at E16 and E19, mice exhibit abnormal kidney development that is more severe than in Pax2^1Neu heterozygotes

• however, kidney development at E13 is normal

kidney medulla hypoplasia ( J:86661 )

abnormal kidney calyx morphology ( J:86661 )

• renal calyces are reduced in size and number compared to in wild-type mice

small kidney ( J:86661 )

• the left kidney is 48% smaller than normal while the right kidney is 58% smaller than normal

decreased nephron number ( J:86661 )

• kidneys contain fewer than normal nephrons with fewer mesenchymal condensates, comma-shaped bodies, and S-shaped bodies and looser mesenchyme adjacent to ureteric bud structures compared to in wild-type kidneys

absent kidney ( J:86661 )

• in 20% of mice

cellular

increased kidney apoptosis ( J:86661 )

• at E16, whole kidney apoptosis is increased compared to in wild-type mice

Genotype
MGI:5442587

cx8

• Allelic Composition: Pax2^1Neu/Pax2⁺; Tg(Hoxb7-EGFP)33Cos/?
• Genetic Background: involves: 102 * C57BL/6 * CBA * CD-1

renal/urinary system

duplex kidney ( J:145105 )

abnormal ureter development ( J:145105 )

• at E12.25, only 12.5% of ureters have begun to separate from their corresponding mesonephric ducts relative to 70% of wild-type ureters, indicating a delay in ureter maturation

• at E14, 25% of ureters remain attached to the mesonephric duct relative to 6.25% of wild-type controls

• at E17, all ureters have independent openings into the bladder; however, their entry is at a less oblique angle relative to that in wild-type controls

• at E17, only 18% of embryos have ureters that enter the bladder at an oblique angle relative to 69% of wild-type controls

• no differences in crown-rump lengths are observed, suggesting a urinary tract specific delay

• delay in ureter maturation is not due to a altered apoptosis in the common nephric duct or surrounding tissues at E11

abnormal ureteric bud morphology ( J:145105 )

• at E10.25, some ureteric buds display irregular contours relative to wild-type controls

impaired branching involved in ureteric bud morphogenesis ( J:145105 )

• at E11.25 and E13, reduced ureteric bud branching may be observed in embryos with a duplex collecting system

ectopic ureteric bud ( J:145105 )

• at E10.25, embryos exhibit more caudally positioned ureteric buds relative to wild-type controls