Organ Weights in Mutant Mice Partly Normalized by Various Pharmacological Treatment Approaches.

Niemann-Pick Type C1 (NPC1, MIM 257220) is a rare, progressive, lethal, inherited autosomal-recessive endolysosomal storage disease caused by mutations in the leading to intracellular lipid storage. We analyzed mostly not jet known alterations of the weights of 14 different organs in the BALB/cNctr-/-J Jackson mice in female and male and mice under various treatment strategies. Mice were treated with (i) no therapy, (ii) vehicle injection, (iii) a combination of miglustat, allopregnanolone, and 2-hydroxypropyl-ß-cyclodextrin (HPßCD), (iv) miglustat, and (v) HPßCD alone starting at P7 and repeated weekly throughout life. The 12 respective male and female wild-type mice groups were evaluated in parallel. In total, 351 mice (176 , 175 ) were dissected at P65. In both sexes, the body weights of None and Sham mice were lower than those of respective mice. The influence of the mutation and/or sex on the weights of various organs, however, differed considerably. In males, and mice had comparable absolute weights of lungs, spleen, and adrenal glands. In mice, smaller weights of hearts, livers, kidneys, testes, vesicular, and scent glands were found. In female mice, ovaries, and uteri were significantly smaller. In mice, relative organ weights, i.e., normalized with body weights, were sex-specifically altered to different extents by the different therapies. The combination of miglustat, allopregnanolone, and the sterol chelator HPßCD partly normalized the weights of more organs than miglustat or HPßCD mono-therapies.