Phenotypes associated with this allele

• Allele Symbol: Lcat^tm1Hgc
• Allele Name: targeted mutation 1, Edward M Rubin
• Allele ID: MGI:2180695
• Summary: 7 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Lcat^tm1Hgc/Lcat^tm1Hgc	involves: 129 * C57BL/6 * C57BL/6J * SJL	MGI:4358715
hm2	Lcat^tm1Hgc/Lcat^tm1Hgc	involves: 129P2/OlaHsd * C57BL/6 * DBA	MGI:4358711
hm3	Lcat^tm1Hgc/Lcat^tm1Hgc	involves: C57BL/6 * DBA	MGI:4358704
ht4	Lcat^tm1Hgc/Lcat^+	involves: C57BL/6 * DBA	MGI:4358705
cx5	Lcat^tm1Hgc/Lcat^tm1Hgc Tg(SREBP1a)7343Reh/?	involves: 129 * C57BL/6 * C57BL/6J * SJL	MGI:4358712
cx6	Lcat^tm1Hgc/Lcat^tm1Hgc Ldlr^tm1Her/Ldlr^tm1Her	involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6 * DBA	MGI:4358708
cx7	Apoe^tm1Unc/Apoe^tm1Unc Lcat^tm1Hgc/Lcat^tm1Hgc	involves: 129P2/OlaHsd * C57BL/6 * DBA	MGI:4358706

Genotype
MGI:4358715

hm1

• Allelic Composition: Lcat^tm1Hgc/Lcat^tm1Hgc
• Genetic Background: involves: 129 * C57BL/6 * C57BL/6J * SJL

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

renal/urinary system

abnormal renal glomerulus morphology ( J:93775 )

• occasional foci of mild arteriolar hyalinosis

• at 16 months of age, occasional mesangial and glomerular epithelial osmiophilic inclusions are seen, many of which have a swirled lamellar appearance

increased mesangial cell number ( J:93775 )

• occasional foci of mild mesangial hypercellularity are seen

expanded mesangial matrix ( J:93775 )

• focal mild mesangial matrix expansion

cellular

increased mesangial cell number ( J:93775 )

• occasional foci of mild mesangial hypercellularity are seen

Genotype
MGI:4358711

hm2

• Allelic Composition: Lcat^tm1Hgc/Lcat^tm1Hgc
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * DBA

homeostasis/metabolism

abnormal circulating protein level ( J:75567 )

• moderate decrease in APOA1 level

• increase in the levels of APOE, APOB-48 and APOB-100

abnormal lipid homeostasis ( J:75567 )

• all HDL particles are in the pre-beta to small HDL size range unlike in controls

abnormal cholesterol homeostasis ( J:75567 )

• about a 9 fold increase in the free cholesterol/esterfied cholesterol ratio compared to wild-type controls

• most of the cholesterol that is present is distributed in the VLDL size range

• there is a 2.6 fold increase in the ratio of saturated + monounsaturated/polyunsaturated cholesterol ester fatty acid species compared to wild-type controls

decreased circulating HDL cholesterol level ( J:75567 )

• very little of the plasma cholesterol is HDL cholesterol

Genotype
MGI:4358704

hm3

• Allelic Composition: Lcat^tm1Hgc/Lcat^tm1Hgc
• Genetic Background: involves: C57BL/6 * DBA

Plasma lipoprotein fractions of Lcat^tm1Hgc/Lcat^tm1Hgc mice contain smaller VLDL particles and complex HDL particles

homeostasis/metabolism

abnormal circulating protein level ( J:41208 )

• plasma APOA1 levels are reduced to 19% of controls

abnormal lipid homeostasis ( J:41208 )

• the lipoprotein size distribution lacks the normal unimodal size distribution and instead has a complex pattern similar to that seen in humans with LCAT deficiency

• the mean diameter of VLDL particles is reduced compared to wild-type controls and notched particles are present

• unlike control particles, HDL particles are morphologically complex and discoidal particles that form classical rouleaux structures are seen

abnormal lipid level ( J:41208 )

• staining of adrenal glands with Oil Red O indicates an absence of stored lipids

decreased cholesterol level ( J:41208 )

• adrenal glands show a 61%, 82% and 30% reduction in total cholesterol, cholesterol ester and unesterified cholesterol levels, respectively

decreased circulating cholesterol level ( J:41208 )

• about a 70% reduction in plasma total cholesterol

• plasma cholesterol ester levels are about 9% that of controls

• however, plasma unesterified cholesterol levels are similar to controls

decreased circulating HDL cholesterol level ( J:41208 )

• about a 92% decrease in plasma HDL cholesterol

• profound decrease in HDL-cholesterol ester levels and a less dramatic decrease in HDL- unesterified cholesterol levels

increased cholesterol level ( J:41208 )

• spleen unesterified cholesterol levels are increased by 21% compared to controls

endocrine/exocrine glands

abnormal adrenal gland morphology ( J:41208 )

• after perfusion adrenal glands appear brown and translucent rather than pearly white as in controls

Genotype
MGI:4358705

ht4

• Allelic Composition: Lcat^tm1Hgc/Lcat⁺
• Genetic Background: involves: C57BL/6 * DBA

homeostasis/metabolism

decreased circulating cholesterol level ( J:41208 )

• slight but significant decrease in plasma total cholesterol and cholesterol ester levels compared to controls

abnormal circulating protein level ( J:41208 )

• plasma APOA1 levels are reduced to 86% of controls

Genotype
MGI:4358712

cx5

• Allelic Composition: Lcat^tm1Hgc/Lcat^tm1Hgc; Tg(SREBP1a)7343Reh/?
• Genetic Background: involves: 129 * C57BL/6 * C57BL/6J * SJL

homeostasis/metabolism

abnormal lipid homeostasis ( J:93775 )

• the VLDL sized particles are largely devoid of triglycerides and highly enriched for free cholesterol and phospholipids

• non-HDL fractions are dominated by large sized, irregularly shaped vesicles that are not seen in transgenic mice wild-type for Lcat

decreased circulating HDL cholesterol level ( J:93775 )

• severely reduced similar to what is seen in Lcat single mutants

decreased circulating LDL cholesterol level ( J:93775 )

• decrease in the LDL/IDL fractions compared to transgenic mice wild-type for Lcat

increased circulating cholesterol level ( J:93775 )

• increase in free cholesterol levels

• increase is largely concentrated in the large VLDL fractions

increased circulating VLDL cholesterol level ( J:93775 )

• accumulation of cholesterol in the large VLDL sized fractions

increased circulating phospholipid level ( J:93775 )

• increase is largely concentrated in the large VLDL fractions

decreased circulating triglyceride level ( J:93775 )

• near absence of plasma triglycerides

albuminuria ( J:93775 )

• present in double mutants but not in transgenic mice wild-type for Lcat

renal/urinary system

albuminuria ( J:93775 )

• present in double mutants but not in transgenic mice wild-type for Lcat

abnormal podocyte morphology ( J:93775 )

• at 10 months of age several podocytes are seen that contain osmiophilic inclusions

podocyte foot process effacement ( J:93775 )

• associated with the presence of adjacent osmiophilic inclusions

abnormal renal glomerulus morphology ( J:93775 )

• about 25% of glomeruli show segmental foam cell infiltrates which preferentially involve the glomerular vascular poles in 60% of the cases

• many glomerular capillary loops show decreased patency due to mesangial encroachment

• diffuse glomerular arteriolar hyalinosis is detected

• at 10 months of age, large focal accumulations of neutral lipids are seen in more than 50% of the glomeruli

• from 6 to 10 months of age mice show progression with fewer lipid deposits and evidence of chronic mesangial injury

abnormal glomerular capillary morphology ( J:93775 )

• many glomerular capillary loops show decreased patency due to mesangial encroachment

increased mesangial cell number ( J:93775 )

• mice with foam cell infiltrates also show a diffuse mild to moderate and focally marked increase in mesangial cellularity, occasionally forming mesangial nodules

expanded mesangial matrix ( J:93775 )

• mice with foam cell infiltrates also show diffuse moderate increases in mesangial matrix

• at 10 months of age several foci of mesangial hyalinosis are seen

glomerulosclerosis ( J:93775 )

• from 6 to 10 months of age mice display progressive glomerulosclerosis

abnormal renal tubule morphology ( J:93775 )

• ultrastructural evidence of tubulointerstitial accumulation of lipid deposits is seen at 10 months of age

abnormal proximal convoluted tubule morphology ( J:93775 )

• some proximal tubule epithelial cells contain intracellular protein re-absorption droplets

• osmiophilic inclusions are seen in proximal tubule epithelial cell adjacent to the basement membrane and in the cortical interstitium

liver/biliary system

enlarged liver ( J:93775 )

cardiovascular system

abnormal glomerular capillary morphology ( J:93775 )

• many glomerular capillary loops show decreased patency due to mesangial encroachment

cellular

increased mesangial cell number ( J:93775 )

• mice with foam cell infiltrates also show a diffuse mild to moderate and focally marked increase in mesangial cellularity, occasionally forming mesangial nodules

growth/size/body

enlarged liver ( J:93775 )

Genotype
MGI:4358708

cx6

• Allelic Composition: Lcat^tm1Hgc/Lcat^tm1Hgc; Ldlr^tm1Her/Ldlr^tm1Her
• Genetic Background: involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6 * DBA

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:75567 )

N • unlike Lcat single mutants, the free cholesterol/esterfied cholesterol ratio is not significantly different from controls

decreased circulating glucose level ( J:89015 )

• fasting glucose levels are 31% lower than the single mutant controls

decreased circulating insulin level ( J:89015 )

• fasting insulin levels are 42% lower than the single mutant controls

abnormal circulating protein level ( J:75567 )

• increase in APOB-100

abnormal lipid homeostasis ( J:75567 , J:89015 )

• about a 2 fold decrease in all plasma lipid constituents compared to mice homozygous null for Lcat and Apoe (J:75567)

• unlike in Ldlr single mutants, the long chain PUFA, 20:4, 20:5 n-3 and 22:6 n-3 esters are absent (J:75567)

• 8 fold increase in triglyceride production rate compared to single mutant controls (J:89015)

increased circulating triglyceride level ( J:75567 , J:89015 )

• increase in plasma triglyceride levels compared to Ldlr single mutants (J:75567)

• 1.7 fold increase in fasting triglyceride levels compared to single mutant littermate controls (J:89015)

• most of the excess triglycerides are concentrated in the VLDL fractions; however, both the LDL and IDL fractions are enriched for triglycerides (J:89015)

abnormal cholesterol homeostasis ( J:75567 , J:89015 )

• compared to Ldlr single mutants the APOB lipoprotein cholesterol ester composition has increases in the 16:0, 18:0, and 18:1 esters and decreases in the 18:2 esters (J:75567)

• there is a 7 fold increase in the ratio of saturated + monounsaturated/polyunsaturated cholesterol ester fatty acid species compared to controls (J:75567)

• total plasma free cholesterol : cholesterol ester ratio is significantly increased compared to controls (J:89015)

decreased circulating HDL cholesterol level ( J:75567 , J:89015 )

• no detectable HDL (J:75567)

• severely reduced (J:89015)

decreased circulating LDL cholesterol level ( J:89015 )

• decrease in the LDL/IDL fractions compared to controls

increased circulating cholesterol level ( J:75567 )

• increase in free cholesterol level compared to Ldlr single mutants

increased circulating VLDL cholesterol level ( J:75567 , J:89015 )

• increase in the cholesterol level in the VLDL fraction (J:89015)

decreased lipoprotein lipase activity ( J:89015 )

• decrease in post heparin lipase activity

Genotype
MGI:4358706

cx7

• Allelic Composition: Apoe^tm1Unc/Apoe^tm1Unc; Lcat^tm1Hgc/Lcat^tm1Hgc
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * DBA

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:75567 )

N • unlike Lcat single mutants, the free cholesterol/esterfied cholesterol ratio is not significantly different from controls

abnormal circulating protein level ( J:75567 )

• increase in APOB-48

abnormal lipid homeostasis ( J:75567 )

• about a 2 fold increase in all plasma lipid constituents compared to mice homozygous null for Lcat and Ldlr

• compared to Apoe single mutants the percentage of long chain PUFA in the total APOB lipoprotein cholesterol ester fraction is decreased

abnormal cholesterol homeostasis ( J:75567 )

• compared to Apoe single mutants cholesteryl stearate and oleate levels are increased 46% and 22%, respectively

• there is a 1.6 fold increase in the ratio of saturated + monounsaturated/polyunsaturated cholesterol ester fatty acid species compared to Apoe single mutants