NPC1 Deficiency in Mice is Associated with Fetal Growth Restriction, Neonatal Lethality and Abnormal Lung Pathology.

ABSTRACT: The rare lysosomal storage disorder Niemann-Pick disease type C1 (NPC1) arises from mutation of NPC1, which encodes a lysosomal transmembrane protein essential for normal transport and trafficking of cholesterol and sphingolipids. NPC1 is highly heterogeneous in both clinical phenotypes and age of onset. Previous studies have reported sub-Mendelian survival rates for mice homozygous for various Npc1 mutant alleles but have not studied the potential mechanisms underlying this phenotype. We performed the first developmental analysis of a Npc1 mouse model, Npc1^em1Pav, and discovered significant fetal growth restriction in homozygous mutants beginning at E16.5. Npc1^{em1Pav/em1Pav} mice also exhibited cyanosis, increased respiratory effort,

SUBMITTER: Rodriguez-Gil JL 

PROVIDER: S-EPMC7019814 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature