Phenotypes associated with this allele

• Allele Symbol: Nphp1^em1Lisu
• Allele Name: endonuclease-mediated mutation 1, Liangzhong Sun
• Allele ID: MGI:7280685
• Summary: 1 genotype

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Nphp1^em1Lisu/Nphp1^em1Lisu	C57BL/6J-Nphp1^em1Lisu	MGI:7280905

Genotype
MGI:7280905

hm1

• Allelic Composition: Nphp1^em1Lisu/Nphp1^em1Lisu
• Genetic Background: C57BL/6J-Nphp1^em1Lisu

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

renal/urinary system

abnormal kidney morphology ( J:324503 )

• renal histology shows characteristic features of nephronophthisis at 8 weeks of age

• however, renal size is normal at 36 and 72 weeks of age

• treatment of 5-week-old mice with an adenovirus expressing Nphp1 reverses the cystic renal phenotype, reduces tubular dilation, and improves glomerulosclerosis, tubulointerstitial fibrosis and urine concentrating capacity

kidney corticomedullary cyst ( J:324503 )

• 8-week-old mice exhibit multiple cysts of different sizes at the corticomedullary junction

glomerulosclerosis ( J:324503 )

• glomerulosclerosis is seen in 72-week-old mice, with poorer vascular patency and periglomerular fibrosis

abnormal renal tubule morphology ( J:324503 )

• segmental thickening and layering of tubular basement membranes

renal tubule hypertrophy ( J:324503 )

• hypertrophied tubules are evident in 8-week-old mice

renal fibrosis ( J:324503 )

• tubulointerstitial fibrotic changes are seen by 36 weeks of age and become much more prominent by 72 weeks

isosthenuria ( J:324503 )

• 5-week-old mice show an increase in 24-hour urine output and a decrease in urine specific gravity, indicating impaired tubular urine concentrating capacity

decreased urine output ( J:324503 )

• 5-week-old mice show an increase in 24-hour urine output

vision/eye

photoreceptor inner segment degeneration ( J:324503 )

photoreceptor outer segment degeneration ( J:324503 )

disorganized retina inner nuclear layer ( J:324503 )

• due to severely abnormal outer plexiform layer, the arrangement of the inner nuclear layer is disorganized and its compactness disappears

retina outer nuclear layer degeneration ( J:324503 )

thin retina outer plexiform layer ( J:324503 )

• hardly any existing outer plexiform layer in 12-week-old mice

retina degeneration ( J:324503 )

• the outer segment, inner segment and outer nuclear layers are completely absent in the retina of 12-week-old mice, with hardly any existing outer plexiform layer

• treatment of 5-week-old mice with an adenovirus expressing Nphp1 results in only a minor restoration of the inner nuclear layer and the loss of the outer and inner segments and the outer nuclear layer are not reversed at 5 weeks of age

reproductive system

decreased male germ cell number ( J:324503 )

• the number of spermatogonia, spermatocytes, and spermatids are reduced in 12-week-old males, and degenerated spermatogenic cells slough off into the seminiferous tubule lumen

• however, testis weights of 12-week-old males are normal

abnormal spermatogenesis ( J:324503 )

• elongating spermatids exist sporadically, with bizarre heads and usually no or only rudimentary tails, indicating an incomplete maturation process

homeostasis/metabolism

increased circulating creatinine level ( J:324503 )

• 72-week-old mice show an elevation in serum urea and creatinine concentrations

• 12-week-old mice show a non-significant but lower trend of serum urea and creatinine concentrations

growth/size/body

kidney corticomedullary cyst ( J:324503 )

• 8-week-old mice exhibit multiple cysts of different sizes at the corticomedullary junction

cellular

decreased male germ cell number ( J:324503 )

• the number of spermatogonia, spermatocytes, and spermatids are reduced in 12-week-old males, and degenerated spermatogenic cells slough off into the seminiferous tubule lumen

• however, testis weights of 12-week-old males are normal

nervous system

photoreceptor inner segment degeneration ( J:324503 )

photoreceptor outer segment degeneration ( J:324503 )

cardiovascular system

cardiovascular system phenotype ( J:324503 )

N • dextrocardia is not seen and hearts do not show septal defect

limbs/digits/tail

limbs/digits/tail phenotype ( J:324503 )

N • no polydactyly is seen

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
nephronophthisis 1		DOID:0111112	OMIM:256100	J:324503