immune system phenotype

• increased susceptibility to bacterial infection
  • following infection with S. pneumoniae, mice exhibit decreased survival compared to similarly treated wild-type mice
  (MGI Ref ID J:136946)

mortality/aging

• increased sensitivity to induced morbidity/mortality
  • following infection with S. pneumoniae, mice exhibit decreased survival compared to similarly treated wild-type mice
  (MGI Ref ID J:136946)

homeostasis/metabolism phenotype

• abnormal homeostasis
  • heterozygotes are overtly normal but express reduced levels of ASGR1 protein, and clear asialoorosomucoid with intermediate efficiency from their circulation relative to wild-type
  (MGI Ref ID J:21380)
  • however, similar to wild-type mice, heterozygotes fail to clear non-desialylated (125)I-labeled orosomucoid
  (MGI Ref ID J:21380)

homeostasis/metabolism phenotype

• abnormal homeostasis
  • however, similar to wild-type mice, homozygotes fail to clear non-desialylated (125)I-labeled orosomucoid
  (MGI Ref ID J:21380)
  • (not mediated by residual ASGR1)
  (MGI Ref ID J:35142)
  • although homozygotes still express some residual ASGR1 protein, they are completely unable to clear asialoorosomucoid from their circulation
  (MGI Ref ID J:21380)
  • notably, homozygotes exhibit significantly reduced ASGR1 protein expression in the presence of normal ASGR1 mRNA levels
  (MGI Ref ID J:21380)
  • the residual ASGR1 is expressed at the hepatocellular surface but fails to effectively remove any one of three different radiolabeled ligands within 30 minutes; mutants show a low but detectable residual clearance of 125I-labeled glycoproteins at 4 hours (not mediated by residual ASGR1)
  (MGI Ref ID J:35142)

mammalian phenotype

• homeostasis/metabolism phenotype
  • Normal - homozygotes are viable, fertile, overtly normal, and display no significant accumulation of desialylated glycoproteins or chylomicron remnants in their plasma
  (MGI Ref ID J:21380)
  • Normal - at 6 weeks to 6 months, homozygotes display normal levels of low density lipoprotein receptor-related protein 1 (LRP1)
  (MGI Ref ID J:35142)
  • Normal - in the total absence of normal ASGR function, homozygotes exhibit normal serum concentrations of galactose-terminating glycoproteins; however, other cross-competing endogenous ASGR ligands accumulate in serum
  (MGI Ref ID J:35142)