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Phenotypes Associated with This Genotype
Genotype
MGI:2451081
Allelic
Composition
Lipatm1Ggb/Lipatm1Ggb
Genetic
Background
involves: 129P2/OlaHsd * CF-1
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Lipatm1Ggb mutation (0 available); any Lipa mutation (17 available)
phenotype observed in females
phenotype observed in males
N normal phenotype

Lipid storage in the liver and small intestine and decrease in subcutaneous white adipose tissue in Lipatm1Ggb/Lipatm1Ggb mice as they age

mortality/aging
• appear normal at birth and survive into adulthood but die at ages of 7-8 months

liver/biliary system
• livers were yellow early with the color deepening to orange with age
• mild compression of sinusoidal spaces
• progressive cholesteryl ester and triglyceride storage in Kupffer cells
• by 3-8 months, significant hypertrophy and hyperplasia of Kupffer cells
• progressive hepatosplenomegaly with age
• heavier than normal livers (J:49674)
• liver weight increased 6 fold over controls at 8 months of age (J:68812)
• cholesterol esters were elevated 32 fold in the liver
• slightly enlarged (J:49674)
• vacuolated with oil drops and isotrophic crystals (J:49674)
• significant vacuolation and neutral lipid storage in hepatocytes at 1.5 months (J:68812)
• percentage of storage cells that are hepatocytes decreases with age with a switch to predominantly Kupffer cell storage by 3-8 months (J:68812)
• lipid storage cells in liver appear to be macrophage
• lipid is mostly in lysosomes

immune system
• progressive cholesteryl ester and triglyceride storage in Kupffer cells
• by 3-8 months, significant hypertrophy and hyperplasia of Kupffer cells
• massive neutral lipid accumulation in bronchoalveolar macrophages evident at 2 months or later
• at 2 months, bronchoalveolar macrophages appear foamy; some alveolar macrophages aggregate to form small patches and fill the alveolar lumen
• fewer bronchoalveolar macrophages are found at 2 months but steadily increase in number with age progression
• yellow in color (J:49674)
• cholesterol esters much elevated (J:49674)
• triglyceride levels decreased (J:49674)
• accumulation of lipid storage cells in spleen at 6 months (J:68812)
• splenomegaly first noted at 3 months
• progressive hepatosplenomegaly with age
• progressive hepatosplenomegaly with age
• heavier than normal (J:49674)
• spleen weight increased 4.4X of controls at 8 months of age (J:68812)
• enlargement of a single mesenteric lymph node at 2 months due to lipid storage in macrophages
• size may be up to 2.5g
• chronic inflammation in the lung
• progressive neutrophil infiltration in the alveolar region first evident at 2 months of age
• steady increase in the number of foamy bronchoalveolar macrophages from 2 to 6 months of age

homeostasis/metabolism
• plasma insulin levels increased 6.7X after glucose load for 30 min
• significantly increased insulin resistance
• lower basal glucose levels
• glucose levels after glucose loading about equivalent to that seen in controls
• tissue storage of cholesteryl ester and triglyceride progressively increases with age
• however, plasma cholesterol and triglyceride levels are normal
• decreased HDL levels and HDL with faster electrophoretic mobility
• after overnight fasting, plasma nonesterified fatty acid levels are significantly elevated at both 2 and 4 months of age
• cholesterol esters were elevated 32 fold in the liver

adipose tissue
• subcutaneous white adipose tissue is present at 1.5 months but decreases significantly at 5 months and disappears by 8 months
• significant reduction of white adipose tissue at 1.5 months with marked size heterogeneity in adipocytes
• undetectable white adipose tissue at 4 months
• at 4 months, brown adipose tissue is histologically similar to white adipose tissue with increased lipid droplet size in the cells
• lacked brown fat at 6 months although it was present at 1 month
• however, no significant differences in nonstressed and stressed core body temperature relative to wild-type
• increased lipid droplet size in brown fat cells
• marked size heterogeneity in adipocytes at 1.5 months of age
• significant reduction in the amount of epididymal fat at 6 months
• complete absence of inguinal white adipose tissue at 6 months
• complete absence of retroperitoneal white adipose tissue at 6 months
• complete absence of interscapular white adipose tissue at 6 months

digestive/alimentary system
• cholesterol esters were considerably elevated
• vacuolation and oil drops seen in villi of the mucosal lining
• progressive discoloration of the small intestine in a proximal to distal fashion
• progressive lipid storage in the small intestine with increasing age
• the duodenum displays a yellow color with increasing age
• the jejunum displays a cream white color with increasing age
• progressive lipid storage in lamina propria of intestinal villi in cells that are proliferated macrophages

endocrine/exocrine glands
• vacuolation, oil drops and anisotrophic crystals found

renal/urinary system
• paler in color than normal but of normal weight

growth/size/body
• certain founder lines weighed about 15-20% less than controls at 4 weeks
• decreased weight not seen in all lines
• weights were all normal at 8 weeks of age
• heavier than normal livers (J:49674)
• liver weight increased 6 fold over controls at 8 months of age (J:68812)
• splenomegaly first noted at 3 months
• progressive hepatosplenomegaly with age
• progressive hepatosplenomegaly with age
• heavier than normal (J:49674)
• spleen weight increased 4.4X of controls at 8 months of age (J:68812)

hematopoietic system
• progressive cholesteryl ester and triglyceride storage in Kupffer cells
• by 3-8 months, significant hypertrophy and hyperplasia of Kupffer cells
• massive neutral lipid accumulation in bronchoalveolar macrophages evident at 2 months or later
• at 2 months, bronchoalveolar macrophages appear foamy; some alveolar macrophages aggregate to form small patches and fill the alveolar lumen
• fewer bronchoalveolar macrophages are found at 2 months but steadily increase in number with age progression
• yellow in color (J:49674)
• cholesterol esters much elevated (J:49674)
• triglyceride levels decreased (J:49674)
• accumulation of lipid storage cells in spleen at 6 months (J:68812)
• splenomegaly first noted at 3 months
• progressive hepatosplenomegaly with age
• progressive hepatosplenomegaly with age
• heavier than normal (J:49674)
• spleen weight increased 4.4X of controls at 8 months of age (J:68812)

behavior/neurological
• at 4 months, male homozygotes display a similar average body weight relative to wild-type males; however, both male and female homozygotes exhibit a significantly higher food intake relative to wild-type

respiratory system
• progressive neutrophil infiltration in the alveolar region first evident at 2 months of age
• steady increase in the number of foamy bronchoalveolar macrophages from 2 to 6 months of age
• accumulation of lipid storage cells in lung macrophages at 6 months
• massive neutral lipid accumulation in bronchoalveolar macrophages evident at 2 months or later
• at 2 months, bronchoalveolar macrophages appear foamy; some alveolar macrophages aggregate to form small patches and fill the alveolar lumen
• fewer bronchoalveolar macrophages are found at 2 months but steadily increase in number with age progression
• striking Clara cell hypertrophy and hyperplasia in the conducting airways at 6 months
• severe alveolar structure remodeling and cell proliferation is evident in larger areas by 6 months
• at 2 months, some small alveolar areas display minor structural remodeling
• massive neutral lipid accumulation in alveolar type II epithelial cells evident at 2 months or later
• at 6 months, the numbers of alveolar type II epithelial cells are increased in areas of alveolar structure remodeling
• increased air space and reduced alveolar surface in some lung areas with age progression
• severe heterogeneous pulmonary emphysema at 6 months

nervous system
• accumulation of lipid storage cells in the epithelium of choroid plexus at 6 months

cardiovascular system
• mild compression of sinusoidal spaces
• progressive cholesteryl ester and triglyceride storage in Kupffer cells
• by 3-8 months, significant hypertrophy and hyperplasia of Kupffer cells

integument
• subcutaneous white adipose tissue is present at 1.5 months but decreases significantly at 5 months and disappears by 8 months

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
lysosomal and lipase deficiency DOID:0080217 OMIM:278000
J:49674
Wolman disease DOID:14497 J:49674


Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB), Gene Ontology (GO)
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last database update
06/28/2022
MGI 6.20
The Jackson Laboratory