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deficient mice also allow us to examine the role of this protein in biliary sterol secretion. The bile is sterol poor and upon stimulation by increasing bile salt excretion, Abcg8/sterolin-2 deficient mice cannot respond, in contrast to the wild-type mice. Thus, Abcg8/sterolin-2 is necessary for cholesterol secretion but not necessary for plant sterol secretion. It could be argued that although the biliary sterol output is comparable to that seen in wild-type mice that this is inappropriately low, since the tissue and plasma pools of sitosterol are so elevated in the knockout mice. Despite this caveat, the findings of sitosterol in significant quantities in the bile suggests that mechanisms other than via the sterolins can 'export' some of these sterols. Interestingly, although humans who are heterozygous for genetic defects in either ABCG5 or ABCG8 seem to be phenotypically normal, mice heterozygous for Abcg8/sterolin-2 deficiency show that sterol secretion is impaired, but not absent. Note that under steady-state conditions on a rodent chow diet, heterozygous animals show no significant elevations in plasma or tissue sitosterol levels, suggesting that the activity of these proteins may not be rate limiting. Furthermore, the heterozygous Abcg8+/- mice showed higher levels of biliary sitosterol relative to the wild-type mice. While the rate of total biliary sterol secretion is reduced compared to wild-type mice, since the heterozygous mice are not sitosterolemic, either the activity of these proteins is not rate limiting or other mechanisms can compensate for a 50% loss of activity. On the other hand, since feeding is intermittent, a slow, but continuous secretion during post-prandial periods could easily negate any mild temporary increase in tissue and plasma plant sterol levels in heterozygous animals. This may be amenable to testing by placing these animals on a high plant sterol diet and measuring the plasma sterol levels."}

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deficient mice also allow us to examine the role of this protein in biliary sterol secretion. The bile is sterol poor and upon stimulation by increasing bile salt excretion, Abcg8/sterolin-2 deficient mice cannot respond, in contrast to the wild-type mice. Thus, Abcg8/sterolin-2 is necessary for cholesterol secretion but not necessary for plant sterol secretion. It could be argued that although the biliary sterol output is comparable to that seen in wild-type mice that this is inappropriately low, since the tissue and plasma pools of sitosterol are so elevated in the knockout mice. Despite this caveat, the findings of sitosterol in significant quantities in the bile suggests that mechanisms other than via the sterolins can 'export' some of these sterols. Interestingly, although humans who are heterozygous for genetic defects in either ABCG5 or ABCG8 seem to be phenotypically normal, mice heterozygous for Abcg8/sterolin-2 deficiency show that sterol secretion is impaired, but not absent. Note that under steady-state conditions on a rodent chow diet, heterozygous animals show no significant elevations in plasma or tissue sitosterol levels, suggesting that the activity of these proteins may not be rate limiting. Furthermore, the heterozygous Abcg8+/- mice showed higher levels of biliary sitosterol relative to the wild-type mice. While the rate of total biliary sterol secretion is reduced compared to wild-type mice, since the heterozygous mice are not sitosterolemic, either the activity of these proteins is not rate limiting or other mechanisms can compensate for a 50% loss of activity. On the other hand, since feeding is intermittent, a slow, but continuous secretion during post-prandial periods could easily negate any mild temporary increase in tissue and plasma plant sterol levels in heterozygous animals. This may be amenable to testing by placing these animals on a high plant sterol diet and measuring the plasma sterol levels."}

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The bile is sterol poor and upon stimulation by increasing bile salt excretion, Abcg8/sterolin-2 deficient mice cannot respond, in contrast to the wild-type mice. Thus, Abcg8/sterolin-2 is necessary for cholesterol secretion but not necessary for plant sterol secretion. It could be argued that although the biliary sterol output is comparable to that seen in wild-type mice that this is inappropriately low, since the tissue and plasma pools of sitosterol are so elevated in the knockout mice. Despite this caveat, the findings of sitosterol in significant quantities in the bile suggests that mechanisms other than via the sterolins can 'export' some of these sterols. Interestingly, although humans who are heterozygous for genetic defects in either ABCG5 or ABCG8 seem to be phenotypically normal, mice heterozygous for Abcg8/sterolin-2 deficiency show that sterol secretion is impaired, but not absent. Note that under steady-state conditions on a rodent chow diet, heterozygous animals show no significant elevations in plasma or tissue sitosterol levels, suggesting that the activity of these proteins may not be rate limiting. Furthermore, the heterozygous Abcg8+/- mice showed higher levels of biliary sitosterol relative to the wild-type mice. While the rate of total biliary sterol secretion is reduced compared to wild-type mice, since the heterozygous mice are not sitosterolemic, either the activity of these proteins is not rate limiting or other mechanisms can compensate for a 50% loss of activity. On the other hand, since feeding is intermittent, a slow, but continuous secretion during post-prandial periods could easily negate any mild temporary increase in tissue and plasma plant sterol levels in heterozygous animals. This may be amenable to testing by placing these animals on a high plant sterol diet and measuring the plasma sterol levels."}