Phenotypes Associated with This Genotype

Genotype
MGI:6456764

• Allelic Composition: Sugct^tm1.2Kald/Sugct^tm1.2Kald
• Genetic Background: B6.Cg-Sugct^tm1.2Kald

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

digestive/alimentary system

abnormal gut flora balance ( J:293423 )

• mice show differences in the proportion of and type of bacteria species in stool, with an increase of firmicutes relative to Bacteroidetes (strongest in Blautia genus containing the families Ruminococcaceae and Lachnospiraceae, then Adlercreutzia genus, Bilophilia genus, and AF12 genus and a decrease in Bifidobacterium genus); microbiome changes resemble those seen in microbiome disbalance in metabolic diseases like diabetes

growth/size/body

increased body weight ( J:293423 )

• 52-week old mice show an increase in body weight

kidney cyst ( J:293423 )

• mice fed a lysine-enriched diet show cystic change in the kidney accompanied with increased renal tubular vacuolation

adipose tissue

abnormal fat cell morphology ( J:293423 )

• aged mice show adipocyte atrophy in the kidney

white adipose tissue inflammation ( J:293423 )

• aged mice show a greater degree of inflammation in epididymal white adipose tissue, often forming crown-like structures

hematopoietic system

increased macrophage cell number ( J:293423 )

• 3-fold increase of macrophages in kidneys of aged mice

• mice fed a lysine-enriched diet show almost a 2.5-fold increase in the number of macrophages in the kidney compared to mutant mice fed a normal diet

homeostasis/metabolism

proteinosis ( J:293423 )

• mice fed a lysine-enriched diet show tubular proteinosis

abnormal lipid metabolism ( J:293423 )

• mice exhibit imbalanced lipid metabolism in the kidney leading to an accumulation of lipids in the kidney

immune system

white adipose tissue inflammation ( J:293423 )

• aged mice show a greater degree of inflammation in epididymal white adipose tissue, often forming crown-like structures

increased macrophage cell number ( J:293423 )

• 3-fold increase of macrophages in kidneys of aged mice

• mice fed a lysine-enriched diet show almost a 2.5-fold increase in the number of macrophages in the kidney compared to mutant mice fed a normal diet

kidney inflammation ( J:293423 )

• 52-week old mice show an increase of interstitial mononuclear cell infiltrate in the kidney, indicating inflammation

• mice fed a lysine-enriched diet for 20 weeks show exacerbated interstitial mononuclear cell infiltrate

liver/biliary system

hepatic steatosis ( J:293423 )

• micro- and macrovesicular steatosis in the liver of aged mice

renal/urinary system

abnormal kidney morphology ( J:293423 )

• lipid accumulation in the kidney of aged mice

• kidney shows an 11-fold increase in glutarate levels and an increase in indoleacrylic acid levels

• however, no changes were seen in acetylcarnitine, 3-hydroxyglutarate, glutarylcarnitine, or glutarylglycine in the kidney

• mice fed a lysine-enriched diet show a further increase in lipid accumulation in the kidney

• mice fed a lysine-enriched diet for 20 weeks show aggravated kidney changes compared to controls, with exacerbated interstitial mononuclear cell infiltrate, medullary tubule mineralization, tubular proteinosis, tubule dilation, and cystic change accompanied with increased renal tubular vacuolation

kidney cyst ( J:293423 )

• mice fed a lysine-enriched diet show cystic change in the kidney accompanied with increased renal tubular vacuolation

abnormal renal tubule epithelium morphology ( J:293423 )

• kidneys show an increase in number of vesicles in cytoplasm of renal tubular epithelial cells in a subset of mice

abnormal kidney medulla morphology ( J:293423 )

• mice fed a lysine-enriched diet show medullary tubule mineralization

dilated renal tubule ( J:293423 )

• mice fed a lysine-enriched diet show tubule dilation

abnormal kidney physiology ( J:293423 )

• mice show imbalanced lipid and acylcarnitine metabolism in kidney

• antibiotic treatment to clear the gut microflora eliminates the metabolic differences

kidney inflammation ( J:293423 )

• 52-week old mice show an increase of interstitial mononuclear cell infiltrate in the kidney, indicating inflammation

• mice fed a lysine-enriched diet for 20 weeks show exacerbated interstitial mononuclear cell infiltrate

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
glutaric acidemia type 3		DOID:0112246	OMIM:231690	J:293423