Phenotypes Associated with This Genotype

Genotype
MGI:3530620

• Allelic Composition: Lcat^tm1Nsa/Lcat^tm1Nsa
• Genetic Background: involves: 129X1/SvJ * C57BL/6J

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

homeostasis/metabolism

abnormal cholesterol homeostasis ( J:39237 )

• on a regular chow diet, homozygotes show a severe reduction in the apoA-I-containing HDL particles present in plasma relative to wild-type; in contrast, apoA-I-containing pre-beta HDL lipoproteins are significantly increased and very heterogeneous in size

• on a regular chow diet, the size and levels of alpha-migrating lipoproteins are significantly decreased relative to wild-type

• on a regular chow diet, the very low density lipoprotein fractions from homozygotes are enriched in triglycerides

• on a regular chow diet, homozygotes accumulate a smaller, cholesterol-poor apoA-I-containing particle whose major lipids are made of of phospholipids

abnormal lipid level ( J:39237 )

• the plasma concentrations of apoA-I of fasted homozygotes are reduced to ~13% of wild-type male and female levels

decreased circulating cholesterol level ( J:39237 )

• in homozygotes, the plasma concentrations of total cholesterol are reduced to ~24% of wild-type male and female levels

• the cholesteryl ester/total cholesterol ratio in homozygous mutant and wild-type mice are 34-52% and 79-81%, respectively, reflecting loss of LCAT-mediated cholesterol esterification

• after 3 weeks on a high-fat high-cholesterol diet, homozygotes exhibit significantly reduced plasma concentrations of total cholesterol, reflecting lower levels of both proatherogenic apoB-containing lipoproteins as well as HDL, relative to wild-type mice

decreased circulating HDL cholesterol level ( J:39237 )

• in homozygotes, the plasma concentrations of HDL cholesterol are reduced to ~7% of wild-type levels

increased circulating triglyceride level ( J:39237 )

• in male homozygotes, plasma triglyceride concentrations are 112% higher than those of wild-type males

• in female homozygotes, triglyceride levels are not significantly different from those of wild-type females, despite a marked variability in plasma triglyceride concentrations that range from 58 mg/dl to 322 mg/dl

renal/urinary system

renal/urinary system phenotype ( J:39237 )

N • at the age of 2-3 months, analysis of plasma albumin, blood urea nitrogen and creatinine levels shows no evidence of renal insufficiency in mutant mice

vision/eye

vision/eye phenotype ( J:39237 )

N • at the age of 2-3 months, slit lamp analysis shows no evidence of corneal opacities in mutant mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Norum disease		DOID:1391	OMIM:245900	J:39237