Biomedical Engineering Reference
In-Depth Information
observed. Mdr2 is a flippase, functioning to move phospholipids from the inner to
the outer leaflet of the canalicular membrane.
36
,
37
Mdr2 mRNA expression markedly
increases at birth, decreases rapidly after birth, and gradually increases to adult levels
at 1 month of age.
The breast cancer resistance protein (Bcrp/Abcg2) has high expression in mouse
liver
38
before birth, peaks at birth, and after birth, decreases rapidly. At approximately
30 days of age, Bcrp expression in male mice increases, whereas in females it does
not, thus creating a gender difference in expression in adult mice.
38
Bile salt export pump (Bsep) is the main transporter for the hepatobiliary excretion
of bile acids. Targeted inactivation of mouse Bsep gene results in nonprogressive but
persistent intrahepatic cholestasis.
39
Mutation of human BSEP gene is linked to the
etiology of progressive familial intrahepatic cholestasis subtype 2.
40
Bsep mRNA
expression is low before birth in mice, reaches the highest level at birth, decreases to
adult levels by 5 days of age, and remains relatively constant thereafter. In rats, Bsep
is also expressed at relatively high levels at 1 day of age.
32
The adenosine triphosphate (ATP)-binding cassette proteins (Abcg5 and g8) are
expressed predominantly in intestine, where they are important for limiting the ab-
sorption of plant steroids.
41
Abcg5 and Abcg8 are also located in the bile canaliculus
and excrete these compounds into bile. The ontogenic expression of Abcg5 and Abcg8
in liver is very similar. Expression of both is extremely low before birth, increases
markedly at parturition, continuing to increase until day 15, and then decreases to
adult levels that are approximately one-half of that observed on day 15.
20.2.4. Hepatic Efflux into Blood
In contrast to Mrp2, Mrp3, 4, and 6 transport chemicals from liver back into blood
(Figure 20.1). Mrp3 mRNA is lowly expressed until 30 days of age, when expression
peaks (Figure 20.4). Mrp4 is expressed at similar levels at all ages, except at day 0,
the age at which it is most highly expressed.
Mutation in MRP6 is associated with the disease pseudoxanthomia elasticum,
characterized by progressive calcification of elastic fibers in many tissues, especially
the skin.
42
,
43
Ontogenic expression of Mrp6 in mouse liver is nondetectable until day
10, when it reaches peak expression, and decreases thereafter to less than one-half
that in adults.
The organic solute transporters (Ost
) heterodimerize to form a transporter
that moves bile acids from enterocytes into blood.
44
Ost
and
are also expressed in
liver but at lower levels, and are thought to transport bile acids from liver back into
blood.
44
The ontogenic expression of Ost
and
is quite different in mouse liver,
even though they heterodimerize to produce a functional transporter. Ost
and Ost
is expressed
at a low level before birth and is expressed most highly on the day of birth. Ost
decreases after birth, with an intermediate increase on day 15 and further increases
at days 40 and 45, reaching adult expression levels. In contrast, Ost
expression
decreases during the first month of life, although it also depicts the highest expression
at birth.
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