Ontogenetic development and spatial distribution of the ileal apical sodium-dependent bile acid transporter and the ileal lipid-binding protein in apoE knockout and C57BL/6 mice.
BACKGROUND
Although apoE-/- mice are characterized by hypercholesterolemia, the bile acid enterohepatic circulation, which plays a crucial role in cholesterol homeostasis, has not been examined in these mice. The differences between apoE-/- and C57BL/6 mice in expression of the ileal ASBT and ILBP and in intestinal bile acid absorption were studied.


METHODS
The intestinal tissues of the fetal, neonatal and post-weaning mice were processed for immunohistochemistry. Body retention and fecal excretion of 75SeHCAT were measured. The bile acid pool size and its composition were analysed by HPLC.


RESULTS
In apoE-/- and C57BL/6 mice, the bile acid pool size was 75 +/- 13 and 78 +/- 13 micromol/ 100 g body weight, respectively, while the ratio of cholic acid/beta-muricholic acid was 1.8 +/- 0.3 and 1.4 +/- 0.3 (P < 0.05), respectively. The daily body retention of 75SeHCAT was 48% = 1.8% in C57 black mice and 58.4% +/- 2.7% in apoE-/- mice (P < 0.05). In both mouse strains, ASBT expression in the small intestine was found in the near-term fetal and post-weaning mice, while ILBP expression was found in all postnatal mice. In the post-weaning mice, ILBP expression was limited to the distal 25%-30% of the small intestine, while ASBT expression was limited to the distal 18%.


CONCLUSIONS
The bile acid enterohepatic circulation in apoE-/- mice probably does not differ greatly from that in C57BL/6 mice.
Håkansson
P
P
AstraZeneca R&D Mölndal, Discovery, Sweden.
Andersson
I
I
Nyström
S
S
Löfgren
L
L
Amrot
L F
LF
Li
Hong
H
D000818:Animals; D001057:Apolipoproteins E / Q000502:physiology*; D001647:Bile Acids and Salts / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D002784:Cholesterol / Q000097:blood; D019826:Cholic Acid / Q000378:metabolism; D002793:Cholic Acids / Q000378:metabolism; D005260:Female; D007082:Ileum / Q000196:embryology* / Q000254:growth & development / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D007408:Intestinal Absorption / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D029363:Organic Anion Transporters, Sodium-Dependent; D027981:Symporters
D001057:Apolipoproteins E; D001647:Bile Acids and Salts; D002352:Carrier Proteins; D002793:Cholic Acids; D029363:Organic Anion Transporters, Sodium-Dependent; D027981:Symporters; C071908:sodium-bile acid cotransporter; C004821:muricholic acid; D002784:Cholesterol; D019826:Cholic Acid