Genomic modulation of diabetes (db/db) and obese (ob/ob) mutation-induced hypercytolipidemia: cytochemical basis of female reproductive tract involution.
Infertility and hypercytolipidemic utero-ovarian involution are recognized consequences of the diabetes-obesity syndrome (DOS) in C57BL mice with either obese (ob/ob) or diabetes (db/db) single gene mutations. We have evaluated the interdependent deleterious influences of both mutation types and differences in the genomic background on utero-ovarian dysfunction in C57BL mice. Control ( +/?) C57BL mice were matched with littermate ob/ob and db/db mutants expressed on either the /KsJ or /6 background. Both ob/ob and db/db mutations increased body weights of /KsJ and /6 background strains relative to +/? groups. In contrast, uterine and ovarian weights were depressed by ob/ob and db/db mutations relative to +/?, regardless of the background strain, but especially when expressed on the /KsJ background. Functionally, both ob/ob and db/db mutations induced hyperglycemic-hyperinsulinemic states coupled with depressed serum estradiol-17-beta and progesterone concentrations when expressed on a /KsJ background. Microscopic analysis of utero-ovarian tissue samples revealed marked hypercytolipidemia in the follicular granulosa and endometrial epithelial tissue layers of both ob/ob and db/db mutant groups relative to normal +/? cytoarchitecture. The db/db mutation consistently promoted more severe hypercytolipidemic profiles than the ob/ob mutation, regardless of background strain. Thus, the severity of utero-ovarian hypercytolipidemia following the expression of ob/ob and db/db mutations in C57BL mice is influenced, or moderated, by the genomic background on which the mutation is expressed.
Garris
David R
DR
Division of Cell Biology and Biophysics, Schools of Medicine and Biological Sciences, University of Missouri-Kansas City, 5007 Rockhill Road, Kansas City, MO 64110, USA. garrisd@umkc.edu
Garris
Bryan L
BL
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000473:pathology*; D004848:Epithelium / Q000648:ultrastructure; D004958:Estradiol / Q000097:blood; D005260:Female; D006949:Hyperlipidemias / Q000235:genetics / Q000473:pathology*; D007328:Insulin / Q000097:blood; D051379:Mice; D008820:Mice, Obese; D046529:Microscopy, Electron, Transmission; D009154:Mutation; D009765:Obesity / Q000235:genetics / Q000473:pathology*; D010053:Ovary / Q000473:pathology*; D014599:Uterus / Q000473:pathology*
D001786:Blood Glucose; D007328:Insulin; D004958:Estradiol