Phenotypes associated with this allele

• Allele Symbol: Lama5^tm3Jhm
• Allele Name: targeted mutation 3, Jeffrey H Miner
• Allele ID: MGI:3823246
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Lama5^tm3Jhm/Lama5^tm3Jhm	involves: 129S1/Sv * 129X1/SvJ	MGI:3823250
hm2	Lama5^tm3Jhm/Lama5^tm3Jhm	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA	MGI:5432558
cn3	Lama5^tm3Jhm/Lama5^tm3Jhm Tg(Nphs1-flpo)1Jhm/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA	MGI:5432559
cx4	Lama5^tm3Jhm/Lama5^tm3Jhm Tg(NPHS2-rtTA2*M2)1Jbk/0 Tg(tetO-LAMA5)1Jhm/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA * FVB/N	MGI:5432562

Genotype
MGI:3823250

hm1

• Allelic Composition: Lama5^tm3Jhm/Lama5^tm3Jhm
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

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

mortality/aging

premature death ( J:128225 )

• mice die by day 28

renal/urinary system

increased kidney apoptosis ( J:128225 )

• cystic epithelia exhibit increased apoptosis

polycystic kidney ( J:128225 )

• by P14, mice develop numerous renal cysts

• in some cysts, epithelial cells loss their unilayered orientation and pile up on one another

• most cysts originate from the proximal tubules while others involve cells from the ascending limb of Henle and the collecting duct

• however, cilia are present in cyst epithelial cells and cysts do not form in the liver or pancreas

• cysts epithelial cells lack tubular cell features such as a dense brush border, and the underlying basement membrane is initially uniform, thickened and exhibits overlays of fibrillar collagen deposits at advanced stages

• cystic epithelia exhibit increased cell proliferation and apoptosis

enlarged kidney ( J:128225 )

• in some mice

increased urine protein level ( J:128225 )

• as early as P2 to P4

• protein to creatine levels in the urine are increased compared to in wild-type mice

abnormal renal glomerulus basement membrane morphology ( J:128225 )

• mice exhibit glomerular basement membrane defects such as thickening of the lamina rara interna and splitting

renal interstitial fibrosis ( J:128225 )

• at later ages

dilated renal tubule ( J:128225 )

• as early as P1 to P2

kidney failure ( J:128225 )

• by P21, mice exhibit progressive

homeostasis/metabolism

increased blood urea nitrogen level ( J:128225 )

increased urine protein level ( J:128225 )

• as early as P2 to P4

• protein to creatine levels in the urine are increased compared to in wild-type mice

growth/size/body

polycystic kidney ( J:128225 )

• by P14, mice develop numerous renal cysts

• in some cysts, epithelial cells loss their unilayered orientation and pile up on one another

• most cysts originate from the proximal tubules while others involve cells from the ascending limb of Henle and the collecting duct

• however, cilia are present in cyst epithelial cells and cysts do not form in the liver or pancreas

• cysts epithelial cells lack tubular cell features such as a dense brush border, and the underlying basement membrane is initially uniform, thickened and exhibits overlays of fibrillar collagen deposits at advanced stages

• cystic epithelia exhibit increased cell proliferation and apoptosis

decreased body size ( J:128225 )

enlarged kidney ( J:128225 )

• in some mice

cellular

increased kidney apoptosis ( J:128225 )

• cystic epithelia exhibit increased apoptosis

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
cystic kidney disease		DOID:2975		J:128225

Genotype
MGI:5432558

hm2

• Allelic Composition: Lama5^tm3Jhm/Lama5^tm3Jhm
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA

mortality/aging

premature death ( J:185850 )

• death at 3 to 4 weeks of age

renal/urinary system

polycystic kidney ( J:185850 )

• mice develop polycystic kidney disease (PKD)

increased urine protein level ( J:185850 )

hematuria ( J:185850 )

homeostasis/metabolism

increased urine protein level ( J:185850 )

hematuria ( J:185850 )

growth/size/body

polycystic kidney ( J:185850 )

• mice develop polycystic kidney disease (PKD)

Genotype
MGI:5432559

cn3

• Allelic Composition: Lama5^tm3Jhm/Lama5^tm3Jhm; Tg(Nphs1-flpo)1Jhm/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA

renal/urinary system

renal/urinary system phenotype ( J:185850 )

N • mice do not develop proteinuria, hematuria, or kidney disease (cysts) after several months in contrast to that Lama5^tm3Jhm homozygotes (no FLPo); mice are viable and fertile

Genotype
MGI:5432562

cx4

• Allelic Composition: Lama5^tm3Jhm/Lama5^tm3Jhm; Tg(NPHS2-rtTA2*M2)1Jbk/0; Tg(tetO-LAMA5)1Jhm/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA * FVB/N

renal/urinary system

renal/urinary system phenotype ( J:185850 )

N • when doxycycline is administered from E12 to E15 to pregnant animals, offspring do not develop proteinuria or hematuria, with no kidney disease at least to 6 months of age