Phenotypes associated with this allele

• Allele Symbol: Tg(SREBP1a)7343Reh
• Allele Name: transgene insertion 7343, Robert E Hammer
• Allele ID: MGI:3054654
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cx1	Lcat^tm1Hgc/Lcat^tm1Hgc Tg(SREBP1a)7343Reh/?	involves: 129 * C57BL/6 * C57BL/6J * SJL	MGI:4358712
tg2	Tg(SREBP1a)7343Reh/0	B6.Cg-Tg(SREBP1a)7343Reh	MGI:3801479
tg3	Tg(SREBP1a)7343Reh/0	involves: C57BL/6J * SJL/J	MGI:3801474
tg4	Tg(SREBP1a)7343Reh/0	Not Specified	MGI:3801483
tg5	Tg(SREBP1a)7343Reh/?	involves: 129 * C57BL/6 * C57BL/6J * SJL	MGI:4358714

Genotype
MGI:4358712

cx1

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

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

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:3801479

tg2

• Allelic Composition: Tg(SREBP1a)7343Reh/0
• Genetic Background: B6.Cg-Tg(SREBP1a)7343Reh

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:100328 )

N • despite peripheral insulin resistance, mice exhibit normal non-esterified fatty acid levels in the plasma and do not develop diabetes

increased circulating glucose level ( J:100328 )

• fasting glucose levels are slightly higher than in wild-type mice

increased circulating insulin level ( J:100328 )

• when fed ad libitum and following glucose loading, mice exhibit increased circulating insulin levels

• mice exhibit postprandial hyperinsulinemia

decreased circulating leptin level ( J:100328 )

improved glucose tolerance ( J:100328 )

insulin resistance ( J:100328 )

• mice exhibit peripheral insulin resistance

endocrine/exocrine glands

increased pancreatic beta cell mass ( J:100328 )

• beta cell mass is increased 3-fold compared to in wild-type mice

pancreatic islet hyperplasia ( J:100328 )

liver/biliary system

enlarged liver ( J:100328 )

adipose tissue

lipodystrophy ( J:100328 )

• lipodystrophy (loss and abnormal redistribution of body fat)

growth/size/body

enlarged liver ( J:100328 )

Genotype
MGI:3801474

tg3

• Allelic Composition: Tg(SREBP1a)7343Reh/0
• Genetic Background: involves: C57BL/6J * SJL/J

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:35770 )

N • despite increases in liver lipid synthesis and content after being fed a low carbohydrate/high protein diet for 2 weeks, mice exhibit normal plasma glucose, creatinine, alkaline phophatase, bilirubin, and blood urea nitrogen levels

increased circulating aspartate transaminase level ( J:35770 )

increased circulating serum albumin level ( J:35770 )

increased circulating total protein level ( J:35770 )

abnormal lipid homeostasis ( J:35770 )

• lipid biosynthesis is increased compared to in wild-type mice

decreased circulating triglyceride level ( J:35770 )

• modest

increased liver cholesterol level ( J:35770 )

• after being fed a low carbohydrate/high protein diet for 2 weeks, liver cholesterol levels are increased 4.7-fold compared to in wild-type mice

• however, plasma cholesterol levels are normal

increased liver triglyceride level ( J:35770 )

• after being fed a low carbohydrate/high protein diet for 2 weeks, liver triglyceride levels are increased 21-fold compared to in wild-type mice

liver/biliary system

liver/biliary system phenotype ( J:35770 )

N • despite accumulation of fat in the liver, mice do not exhibit generalized inflammation in the liver or liver necrosis

enlarged liver ( J:35770 )

• after birth, mice exhibit abdominal swelling due to an enlarged liver than continues to enlarge after weaning when mice are placed on a low carbohydrate/high protein diet

• liver enlargement occurs due to increased lipid accumulation

increased liver weight ( J:35770 )

• after being fed a low carbohydrate/high protein diet for 2 weeks, liver weight is increased 4-fold compared to similarly treated wild-type mice

increased liver cholesterol level ( J:35770 )

• after being fed a low carbohydrate/high protein diet for 2 weeks, liver cholesterol levels are increased 4.7-fold compared to in wild-type mice

• however, plasma cholesterol levels are normal

increased liver triglyceride level ( J:35770 )

• after being fed a low carbohydrate/high protein diet for 2 weeks, liver triglyceride levels are increased 21-fold compared to in wild-type mice

abnormal hepatocyte morphology ( J:35770 )

• at 16 weeks of age mice exhibit distended hepatocytes due to fat droplet accumulation

pale liver ( J:35770 )

adipose tissue

abnormal fat pad morphology ( J:35770 )

• mice exhibit a decrease in subcutaneous, omental, perirenal and epididymal fat compared to in wild-type mice

decreased epididymal fat pad weight ( J:35770 )

• after being fed a low carbohydrate/high protein diet for 2 weeks, epididymal fat pad weight is decreased by more than 90% compared to similarly treated wild-type mice

growth/size/body

enlarged liver ( J:35770 )

• after birth, mice exhibit abdominal swelling due to an enlarged liver than continues to enlarge after weaning when mice are placed on a low carbohydrate/high protein diet

• liver enlargement occurs due to increased lipid accumulation

increased liver weight ( J:35770 )

• after being fed a low carbohydrate/high protein diet for 2 weeks, liver weight is increased 4-fold compared to similarly treated wild-type mice

Genotype
MGI:3801483

tg4

• Allelic Composition: Tg(SREBP1a)7343Reh/0
• Genetic Background: Not Specified

liver/biliary system

impaired liver regeneration ( J:129886 )

• after 70% resection, liver regeneration is suppressed due to decreased proliferation compared to in wild-type mice

Genotype
MGI:4358714

tg5

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

homeostasis/metabolism

decreased cholesterol level ( J:93775 )

• significant reduction in cholesterol in all lipoprotein fractions

decreased circulating cholesterol level ( J:93775 )

• decrease in total cholesterol in the plasma

decreased circulating HDL cholesterol level ( J:93775 )

• decrease in total cholesterol is largely the result of a decrease in HDL cholesterol

renal/urinary system

renal/urinary system phenotype ( J:93775 )

N • unlike transgenic mice that are also null for Lcat, no significant ultrastructural kidney abnormalities are detected

abnormal renal glomerulus morphology ( J:93775 )

• occasional foci of mild arteriolar hyalinosis

increased mesangial cell number ( J:93775 )

• occasional foci of mild mesangial hypercellularity are seen

expanded mesangial matrix ( J:93775 )

• focal mild mesangial matrix expansion

liver/biliary system

enlarged liver ( J:93775 )

growth/size/body

enlarged liver ( J:93775 )

cellular

increased mesangial cell number ( J:93775 )

• occasional foci of mild mesangial hypercellularity are seen