Phenotypes associated with this allele

• Allele Symbol: Lgr4^tm1.2Knis
• Allele Name: targeted mutation 1.2, Katsuhiko Nishimori
• Allele ID: MGI:3762641
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Lgr4^tm1.2Knis/Lgr4^tm1.2Knis	B6.129P2-Lgr4^tm1.2Knis	MGI:5438250
hm2	Lgr4^tm1.2Knis/Lgr4^tm1.2Knis	involves: 129P2/OlaHsd * C57BL/6	MGI:3762642
ht3	Lgr4^tm1.2Knis/Lgr4^+	involves: 129P2/OlaHsd * C57BL/6	MGI:3762643

Genotype
MGI:5438250

hm1

• Allelic Composition: Lgr4^tm1.2Knis/Lgr4^tm1.2Knis
• Genetic Background: B6.129P2-Lgr4^tm1.2Knis

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

mortality/aging

perinatal lethality, complete penetrance ( J:172277 )

• at E18.5, half of the few remaining homozygotes (2 of 4) are already dead

• no homozygotes are obtained at E19.5

lethality throughout fetal growth and development, incomplete penetrance ( J:172277 )

• most homozygotes appear to die between E15.5 and E18.5

renal/urinary system

increased kidney apoptosis ( J:186318 )

• at E16.5, apoptosis is significantly induced in the renal peripheral zone, unlike in wild-type kidneys

• however, no significant difference in apoptosis is detected in the ureteric bud

kidney cyst ( J:172277 )

• by E16.5, all metanephric kidneys exhibit cystic changes, as indicated by dilated tubule formation

abnormal metanephric mesenchyme morphology ( J:186318 )

• at E16.5, disruption of the cap mesenchyme is observed

• PAX2-expressing cap mesenchyme is longer detectable at E16.5

abnormal metanephric ureteric bud development ( J:172277 )

• at E15.5, the ureteric bud undergoes premature epithelial differentiation

small metanephros ( J:172277 )

• smaller sized kidneys at E16.5

renal hypoplasia ( J:172277 )

• severe renal hypoplasia by E16.5

impaired branching involved in ureteric bud morphogenesis ( J:172277 )

• at E15.5, impaired ureteric branching morphogenesis is observed, unlike in wild-type control kidneys

cellular

increased kidney apoptosis ( J:186318 )

• at E16.5, apoptosis is significantly induced in the renal peripheral zone, unlike in wild-type kidneys

• however, no significant difference in apoptosis is detected in the ureteric bud

growth/size/body

kidney cyst ( J:172277 )

• by E16.5, all metanephric kidneys exhibit cystic changes, as indicated by dilated tubule formation

Genotype
MGI:3762642

hm2

• Allelic Composition: Lgr4^tm1.2Knis/Lgr4^tm1.2Knis
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

mortality/aging

premature death ( J:127019 )

• the one homozygote that survived past weaning died on P42

lethality throughout fetal growth and development, incomplete penetrance ( J:127019 )

• fewer than expected embryos are found starting at E16.5

• the expected proportion of homozygous embryos is present at E15.5

perinatal lethality, incomplete penetrance ( J:127019 )

• only about half of the expected number of mice are found at birth

neonatal lethality, incomplete penetrance ( J:127019 )

• almost all mice born die within 2 days of birth

growth/size/body

polycystic kidney ( J:127019 )

• the kidneys of the single post-weaning survivor contained multiple, fluid-filled cysts associated with flattened tubular epithelial cells and vacuolar degeneration of these epithelial cells

• at birth, some of the hypoplastic kidneys also show polycystic changes

postnatal growth retardation ( J:127019 )

• the one mouse that survived past weaning showed severe growth retardation

decreased fetal weight ( J:127019 )

• from E14.5 to E19.5 fetal body weight is reduced relative to wild-type and heterozygous littermates

• from E14.5 to E19.5 fetal body weight is about 70% that of wild-type littermates

renal/urinary system

abnormal kidney morphology ( J:127019 )

• subtle asymmetries of the right and left kidney are seen in some mice at birth

• no obvious differences are seen in ureteric bud branching at E13.5

polycystic kidney ( J:127019 )

• the kidneys of the single post-weaning survivor contained multiple, fluid-filled cysts associated with flattened tubular epithelial cells and vacuolar degeneration of these epithelial cells

• at birth, some of the hypoplastic kidneys also show polycystic changes

decreased kidney weight ( J:127019 )

• at birth, average kidney weight is only 0.23% of total body weight compared to 0.51% in wild-type mice

renal hypoplasia ( J:127019 )

• seen at birth

abnormal nephron morphology ( J:127019 )

• at birth, some mice with hypoplastic kidneys also lack functional nephrons

• in more than half of the mice basic glomerular and tubular structure are preserved

decreased renal glomerulus number ( J:127019 )

• reduced in number and in density compared to wild-type mice

homeostasis/metabolism

increased circulating creatinine level ( J:127019 )

• seen in all homozygous mice at birth

vision/eye

eyelids open at birth ( J:126813 )

• seen in all homozygotes as the result of impaired eyelid closure

integument

abnormal keratinocyte physiology ( J:126813 )

• in vitro assays using keratinocytes show a significant delay in healing 3 hours after scratching suggesting reduced keratinocyte motility

• however no change in cell proliferation is detected

Genotype
MGI:3762643

ht3

• Allelic Composition: Lgr4^tm1.2Knis/Lgr4⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

mortality/aging

perinatal lethality, incomplete penetrance ( J:127019 )

• only about 87% of the expected number of mice are found at birth

• a reduction from the excpected number of heterozygous mice is seen at E18.5