Phenotypes associated with this allele

• Allele Symbol: Lgmn^tm1Cptr
• Allele Name: targeted mutation 1, Christoph Peters
• Allele ID: MGI:4415342
• Summary: 1 genotype

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Lgmn^tm1Cptr/Lgmn^tm1Cptr	B6.129S6-Lgmn^tm1Cptr	MGI:4415343

Genotype
MGI:4415343

hm1

• Allelic Composition: Lgmn^tm1Cptr/Lgmn^tm1Cptr
• Genetic Background: B6.129S6-Lgmn^tm1Cptr

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

immune system

enlarged spleen ( J:172774 )

• some splenomegaly is observed

abnormal adaptive immunity ( J:155339 )

• the capacity to initiate an adaptive immune response upon TLR9 activation is impaired, fewer ovalbumin specific T cells in spleen, with no proliferation, after immunization with ovalbumin coated beads and CpG

decreased interleukin-12b secretion ( J:155339 )

• in vivo by dendritic cells after i.v. injection of TLR9 agonist

decreased interleukin-6 secretion ( J:155339 )

• by bone marrow dendritic cells in response to stimulation with a TLR9 agonist but not a TLR4 agonist

• in vivo by dendritic cells after i.v. injection of TLR9 agonist

decreased tumor necrosis factor secretion ( J:155339 )

• by bone marrow dendritic cells in response to stimulation with a TLR9 agonist but not a TLR4 agonist

renal/urinary system

renal glomerulus cyst ( J:172774 )

• glomerular cysts are evident by 10 months of age

increased urine protein level ( J:172774 )

• at 6 months of age, homozygotes exhibit low-MW proteinuria relative to wild-type controls

• mutant urine samples contain higher levels of albumin, transferrin, and angiotensinogen

albuminuria ( J:172774 )

abnormal renal glomerulus morphology ( J:172774 )

• by 10 months of age, proximal tubular cell (PTC) hyperplasia leads to glomerular crowding

kidney cortex atrophy ( J:172774 )

• by 10 months of age, proximal tubular cell (PTC) hyperplasia leads to secondary cortical compression

abnormal kidney interstitium morphology ( J:172774 )

• an expansion of the kidney interstitium with fibrosis is noted by 3 months and progresses with age

renal interstitial fibrosis ( J:172774 )

• by 10 months of age

abnormal kidney outer medulla outer stripe morphology ( J:172774 )

• by 10 months of age, proximal tubular cell (PTC) hyperplasia leads to expansion of the outer stripe of the outer renal medulla

hydronephrosis ( J:172774 )

• dilation of the renal pelvis is eventually observed

renal tubule atrophy ( J:172774 )

• by 10 months of age, tubular atrophy and thickening of peritubular basement membrane is observed

abnormal proximal convoluted tubule morphology ( J:172774 )

• at 2 months of age, kidney proximal tubular cells (PTCs) exhibit hyperplasia with an increase in nuclear size and nucleo-cytoplasmic ratio; some mitotic figures are observed

• PTC hyperplasia is at least in part attributed to increased kidney EGFR expression at 2-3 months but not at 6 months of age

pale kidney ( J:172774 )

• starting at ~2 months of age, mutant kidneys become progressively paler than wild-type

abnormal kidney physiology ( J:172774 )

• homozygotes accumulate a discrete set of proteins in their PTC endosomes and lysosomes, indicating a defect in the normal catabolism of proteins captured from the filtrate

decreased renal glomerular filtration rate ( J:172774 )

• at 6 months of age, the GFR drops from 148 +/- 27 ul/min in wild-type mice to 63 +/- 30 ul/min

cellular

lysosomal protein accumulation ( J:172774 )

• unlike wild-type, mutant kidney lysosomes fail to process some cathepsins to their mature 2-chain forms and accumulate several low-MW proteins indicating defective metabolism of some substrates

homeostasis/metabolism

increased circulating creatinine level ( J:172774 )

• at 6 months of age, plasma creatinine levels are nearly twice those of wild-type controls

increased urine protein level ( J:172774 )

• at 6 months of age, homozygotes exhibit low-MW proteinuria relative to wild-type controls

• mutant urine samples contain higher levels of albumin, transferrin, and angiotensinogen

albuminuria ( J:172774 )

growth/size/body

slow postnatal weight gain ( J:172774 )

• homozygotes fail to gain weight at the same rate as wild-type controls

renal glomerulus cyst ( J:172774 )

• glomerular cysts are evident by 10 months of age

enlarged spleen ( J:172774 )

• some splenomegaly is observed

hematopoietic system

enlarged spleen ( J:172774 )

• some splenomegaly is observed