Phenotypes Associated with This Genotype

Genotype
MGI:5538404

• Allelic Composition: Npc2^tm1Plob/Npc2^tm1Plob
• Genetic Background: involves: 129S1/Sv * BALB/c

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

growth/size/body

decreased body weight ( J:204311 )

increased lung weight ( J:204311 )

• lung weight as a % of total body weight is higher

respiratory system

abnormal lung morphology ( J:204311 )

• lungs contain 'nests' of vacuolar filled macrophages and enlarged foamy alveolar macrophages

• accumulation of tubular myelin and surfactant aggregates in large airways and large surfactant aggregates next to type II cells or in the alveolar space

• accumulation of surfactant is seen as tight or loosely packed whirls of phospholipid-like surfactant material in focal areas of the alveolar spaces, and as the most common form, string-like surfactant

abnormal lung vasculature morphology ( J:204311 )

• enlarged polymorphonuclear leukocytes or circulating macrophages filled with vacuolar inclusions are seen within lung capillaries

• capillary endothelial cells containing enlarged vacuoles/multivesicular bodies are seen in lungs

increased lung weight ( J:204311 )

• lung weight as a % of total body weight is higher

abnormal alveolar macrophage morphology ( J:204311 )

• alveolar macrophages are enlarged and vacuole-filled, some with concentric multilamellar electron dense surfactant-like materials

• alveolar macrophages are laden with free cholesterol with many large, foamy cells; phospholipid levels are elevated 2-fold and cholesterol levels are elevated 8-fold in alveolar macrophage

pulmonary alveolar proteinosis ( J:204311 )

• proteinaceous-like material in the alveolar space

abnormal type II pneumocyte morphology ( J:204311 )

• alveolar type II cells have many autophagosomes

increased alveolar lamellar body number ( J:204311 )

• alveolar type II cells exhibit 65% more lamellar bodies than wild-type cells

small alveolar lamellar bodies ( J:204311 )

• alveolar type II cell lamellar bodies are smaller compared to wild-type mice

thick pulmonary interalveolar septum ( J:204311 )

• increase in alveolar septum thickness

abnormal surfactant composition ( J:204311 )

• increase in surfactant phospholipid levels

hematopoietic system

abnormal alveolar macrophage morphology ( J:204311 )

• alveolar macrophages are enlarged and vacuole-filled, some with concentric multilamellar electron dense surfactant-like materials

• alveolar macrophages are laden with free cholesterol with many large, foamy cells; phospholipid levels are elevated 2-fold and cholesterol levels are elevated 8-fold in alveolar macrophage

homeostasis/metabolism

abnormal lipid level ( J:204311 )

• elevation in lipid content in the lungs

increased cholesterol level ( J:204311 )

• increase in cholesterol content in the lungs

• 35-fold elevation of cholesterol levels of branchoalveolar lavage

• 7.9-fold increase in cholesterol levels in lamellar bodies

abnormal phospholipid level ( J:204311 )

• increase in phospholipid content in the lungs

• 3-fold elevation of phospholipid levels of bronchoalveolar lavage

• 2- to 2.8-fold increase in phospholipid levels in lamellar bodies

lipidosis ( J:204311 )

• lungs exhibit severe surfactant accumulation, indicating alveolar lipidosis

pulmonary alveolar proteinosis ( J:204311 )

• proteinaceous-like material in the alveolar space

immune system

abnormal alveolar macrophage morphology ( J:204311 )

• alveolar macrophages are enlarged and vacuole-filled, some with concentric multilamellar electron dense surfactant-like materials

• alveolar macrophages are laden with free cholesterol with many large, foamy cells; phospholipid levels are elevated 2-fold and cholesterol levels are elevated 8-fold in alveolar macrophage

cardiovascular system

abnormal lung vasculature morphology ( J:204311 )

• enlarged polymorphonuclear leukocytes or circulating macrophages filled with vacuolar inclusions are seen within lung capillaries

• capillary endothelial cells containing enlarged vacuoles/multivesicular bodies are seen in lungs

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Niemann-Pick disease		DOID:14504		J:204311