Abstract
Lith genes control susceptibility to cholesterol gallstone formation in inbred strains of mice on a lithogenic diet containing high fat, high cholesterol and 0.5% cholic acid. Our study defines the physical-chemical phenotypes of C57L, AKR, and (C57L x AKR) F1 mouse gallbladder biles during 56 days on the lithogenic diet. We found enhanced cholesterol supersaturation, accumulation of mucin gel and larger gallbladders in all C57L and F(t) mice, as well as more frequent gallstone formation in male C57L and F(t) mice (80%) compared to females (40%) or AKR mice (15%). In male C57L and F1 mice, mucin gel accumulated at 3 days, followed by cholesterol supersaturation and phase separation of liquid crystals, solid monohydrate crystals, and, in 43% of mice, anhydrous cholesterol crystals; whereas, in females, phase separations were delayed 2 to 9 days, and anhydrous crystals did not form. In AKR, mice, cholesterol supersaturation and phase separations were infrequent and delayed, and gender did not influence the phenotype. Taurocholate invariably replaced endogenous bile salts, especially tauro-β- muricholate, with crystallization sequences matching taurocholate-containing model bile systems. We conclude: i) Lith genes determine biliary, cholesterol snpersaturation, mucin gel accumulation, gallbladder size, phase-separation, and prevalence of cholesterol gallstones. ii) Identical phenotypes in C57L and F1 mice indicate susceptibility to cholesterol gallstones is genetically, dominant, favoring males 2:1. iii) Mucin gel accumulation, crystallization, and stone formation are rare in AKR mice. This definition of the physical chemistry of lithogenesis should aid in further elucidation of the Lith genes and the proteins they encode.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1395-1411 |
| Number of pages | 17 |
| Journal | Journal of Lipid Research |
| Volume | 38 |
| Issue number | 7 |
| State | Published - Jul 1 1997 |
| Externally published | Yes |
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Keywords
- Anhydrous and monohydrate crystals
- Crystallization
- Dominant trait
- Gallbladder size
- Gallstones
- Genetics
- Liquid crystals
- Microscopy
- Mucin gel
- Phase separation
ASJC Scopus subject areas
- Biochemistry
- Endocrinology
- Cell Biology
Cite this
Phenotypic characterization of lith genes that determine susceptibility to cholesterol cholelithiasis in inbred mice : Physical-chemistry of gallbladder bile. / Wang, David Q.H.; Paigen, Beverly; Carey, Martin C.
In: Journal of Lipid Research, Vol. 38, No. 7, 01.07.1997, p. 1395-1411.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Phenotypic characterization of lith genes that determine susceptibility to cholesterol cholelithiasis in inbred mice
T2 - Physical-chemistry of gallbladder bile
AU - Wang, David Q.H.
AU - Paigen, Beverly
AU - Carey, Martin C.
PY - 1997/7/1
Y1 - 1997/7/1
N2 - Lith genes control susceptibility to cholesterol gallstone formation in inbred strains of mice on a lithogenic diet containing high fat, high cholesterol and 0.5% cholic acid. Our study defines the physical-chemical phenotypes of C57L, AKR, and (C57L x AKR) F1 mouse gallbladder biles during 56 days on the lithogenic diet. We found enhanced cholesterol supersaturation, accumulation of mucin gel and larger gallbladders in all C57L and F(t) mice, as well as more frequent gallstone formation in male C57L and F(t) mice (80%) compared to females (40%) or AKR mice (15%). In male C57L and F1 mice, mucin gel accumulated at 3 days, followed by cholesterol supersaturation and phase separation of liquid crystals, solid monohydrate crystals, and, in 43% of mice, anhydrous cholesterol crystals; whereas, in females, phase separations were delayed 2 to 9 days, and anhydrous crystals did not form. In AKR, mice, cholesterol supersaturation and phase separations were infrequent and delayed, and gender did not influence the phenotype. Taurocholate invariably replaced endogenous bile salts, especially tauro-β- muricholate, with crystallization sequences matching taurocholate-containing model bile systems. We conclude: i) Lith genes determine biliary, cholesterol snpersaturation, mucin gel accumulation, gallbladder size, phase-separation, and prevalence of cholesterol gallstones. ii) Identical phenotypes in C57L and F1 mice indicate susceptibility to cholesterol gallstones is genetically, dominant, favoring males 2:1. iii) Mucin gel accumulation, crystallization, and stone formation are rare in AKR mice. This definition of the physical chemistry of lithogenesis should aid in further elucidation of the Lith genes and the proteins they encode.
AB - Lith genes control susceptibility to cholesterol gallstone formation in inbred strains of mice on a lithogenic diet containing high fat, high cholesterol and 0.5% cholic acid. Our study defines the physical-chemical phenotypes of C57L, AKR, and (C57L x AKR) F1 mouse gallbladder biles during 56 days on the lithogenic diet. We found enhanced cholesterol supersaturation, accumulation of mucin gel and larger gallbladders in all C57L and F(t) mice, as well as more frequent gallstone formation in male C57L and F(t) mice (80%) compared to females (40%) or AKR mice (15%). In male C57L and F1 mice, mucin gel accumulated at 3 days, followed by cholesterol supersaturation and phase separation of liquid crystals, solid monohydrate crystals, and, in 43% of mice, anhydrous cholesterol crystals; whereas, in females, phase separations were delayed 2 to 9 days, and anhydrous crystals did not form. In AKR, mice, cholesterol supersaturation and phase separations were infrequent and delayed, and gender did not influence the phenotype. Taurocholate invariably replaced endogenous bile salts, especially tauro-β- muricholate, with crystallization sequences matching taurocholate-containing model bile systems. We conclude: i) Lith genes determine biliary, cholesterol snpersaturation, mucin gel accumulation, gallbladder size, phase-separation, and prevalence of cholesterol gallstones. ii) Identical phenotypes in C57L and F1 mice indicate susceptibility to cholesterol gallstones is genetically, dominant, favoring males 2:1. iii) Mucin gel accumulation, crystallization, and stone formation are rare in AKR mice. This definition of the physical chemistry of lithogenesis should aid in further elucidation of the Lith genes and the proteins they encode.
KW - Anhydrous and monohydrate crystals
KW - Crystallization
KW - Dominant trait
KW - Gallbladder size
KW - Gallstones
KW - Genetics
KW - Liquid crystals
KW - Microscopy
KW - Mucin gel
KW - Phase separation
UR - http://www.scopus.com/inward/record.url?scp=0030810683&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0030810683&partnerID=8YFLogxK
M3 - Article
C2 - 9254065
AN - SCOPUS:0030810683
VL - 38
SP - 1395
EP - 1411
JO - Journal of Lipid Research
JF - Journal of Lipid Research
SN - 0022-2275
IS - 7
ER -