TABLE 6

Ontogeny profile of hepatic efflux transporters in mice based on protein expression and mRNA expression levels

Percentages represent expression/activity relative to adult levels.

Efflux TransporterOnset of Expression/ActivityAdult Levels ReachedAge-Related Changes (% of Adult) in Expression/Activity after BirthCommentsReferences
CERP
 mRNA expressionFetal development (97%–179%)0 daysInconsistent patternAdult age: 60 days. Strain: C57BL/6J (M). Methods: RNA-seq and RT-PCRCui et al. (2012a)
MDR1B
 mRNA expressionFetal development (100%)No changesAdult age: 45 days. Strain: C57BL/6J (mixed). Methods: RNA-seq.Cui et al. (2009)
 Protein expressionNRNRNo changesAdult age: NR. Strain: FVB (NR). Methods: Western blottingMahmood et al. (2001)
MDR2
 mRNA expressionFetal development (∼43%–44% at day −2)1 daysPeaks 1.1–1.5-fold adult levels immediately after birth in M and F, falling back to ∼50% adult levels between days 5–45Adult age: 60 days. Strain: C57BL/6J (M/mixed). Methods: RNA-seqCui et al. (2009, 2012a)
ABCG5
 mRNA expressionFetal development (1.3%)5 daysInconsistent patternStatistical difference in expression between CV and GF strain (Selwyn et al., 2015). Adult age: 60 days (Cui et al., 2012a) and 90 days (Selwyn et al., 2015). Strain: C57BL/6J (Cui et al., 2012a) and CV + GF (Selwyn et al., 2015) (M). Methods: RNA-seq (Cui et al., 2012a) and RT-PCR (Selwyn et al., 2015)Cui et al. (2012a); Selwyn et al. (2015)
 Protein expressionNR (15 days: 1867%–3371%)NRDecreased progressivelyStatistical difference in expression between CV and GF strain. Adult age: 90 days. Strain: CV + GF (M). Methods: Western blottingSelwyn et al. (2015)
ABCG8
 mRNA expressionLow expression in fetal tissue5 daysInconsistent patternAdult age: 60 days (Cui et al., 2012a) and 90 days (Selwyn et al., 2015). Strain: C57BL/6J (Cui et al., 2012a) and CV + GF (Selwyn et al., 2015) (M). Methods: RNA-seq (Cui et al., 2012a) and RT-PCR (Selwyn et al., 2015)Cui et al. (2012a); Selwyn et al. (2015)
 Protein expressionNR (15 days: 208%–4520%)NRDecreased progressivelyStatistical difference in expression between CV and GF strain. Adult age: 90 days. Strain: CV + GF (M). Methods: Western blottingSelwyn et al. (2015)
ATP7B
 mRNA expressionFetal development (280%)25 daysInconsistent patternAdult age: 60 days. Strain: C57BL/6J (M). Methods: RNA-seqCui et al. (2012a)
BCRP
 mRNA expressionFetal development (271%) as measured by RNA sequencing60 daysIncreased slowlyAdult age: 60 days. Strain: C57BL/6J (M). Methods: RNA-seqCui et al. (2012a)
BSEP
 mRNA expressionFetal development (30%)5 daysInconsistent patternAdult age: 56 days (Cheng et al., 2007) and 60 days (Cui et al., 2012a). Strain: C57BL/6J (mixed). Methods: bDNA (Cheng et al., 2007) and RNA-seq (Cui et al., 2012a)Cheng et al. (2007); Cui et al. (2012a)
MATE1
 mRNA expressionFetal development (28%)15 daysIncreased rapidlyAdult age: 60 days. Strain: C57BL/6J (M). Methods: RNA-seqCui et al. (2012a)
MRP1
 mRNA expressionFetal development (558%)25–30 daysDecreased rapidlyAdult age: 60 days. Strain: C57BL/6J (M). Methods: RNA-seqCui et al. (2012a)
MRP2
 mRNA expressionFetal development (30%)10 daysIncreased slowlyAdult age: 45 days (Maher et al., 2005), 60 days (Cui et al., 2012a; Li et al., 2016), and 90 days (Selwyn et al., 2015). Strain: C57BL/6J (Maher et al., 2005; Cui et al., 2012a; Selwyn et al., 2015; Li et al., 2016) (mixed) and CV + GF (Selwyn et al., 2015) (M). Methods: RNA-seq (Cui et al., 2012a), RT-PCR (Selwyn et al., 2015; Li et al., 2016), and bDNA44Maher et al. (2005); Cui et al. (2012a); Selwyn et al. (2015); Li et al. (2016)
MRP3
 mRNA expressionFetal development (26%)30 daysIncreased slowlyAdult age: 45 days (Maher et al., 2005) and 60 days (Cui et al., 2012a; Li et al., 2016). Strain: C57BL/6J (Maher et al., 2005; Cui et al., 2012a; Selwyn et al., 2015; Li et al., 2016) (mixed). Methods: RNA-seq (Cui et al., 2012a), RT-PCR (Selwyn et al., 2015; Li et al., 2016), and bDNA (Maher et al., 2005)Maher et al. (2005); Cui et al. (2012a); Li et al. (2016)
MRP4
 mRNA expressionFetal development (200%)10 daysDecreased slowlyAdult age: 45 days (Maher et al., 2005) and 60 days (Cui et al., 2012a; Li et al., 2016). Strain: C57BL/6J (Maher et al., 2005; Cui et al., 2012a; Selwyn et al., 2015; Li et al., 2016) (mixed). Methods: RNA-seq (Cui et al., 2012a), RT-PCR (Selwyn et al., 2015; Li et al., 2016), and bDNA44Maher et al. (2005); Cui et al. (2012a); Li et al. (2016)
 Protein expressionNRNRIncreased slowlyAdult age: 60 days. Strain: C57BL/6. Methods: Western blottingLi et al. (2016)
MRP5
 mRNA expressionFetal development (1200%)25–30 daysDecreased rapidlyAdult age: 60 days. Strain: C57BL/6J (M). Methods: RNA-seqCui et al. (2012a)
MRP6
 mRNA expressionFetal development (0%–30%)3 daysIncreased rapidlyAdult age: 45 days (Maher et al., 2005) and 60 days (Cui et al., 2012a). Strain: C57BL/6J (mixed). Methods: RNA-seq (Cui et al., 2012a) and bDNA (Maher et al., 2005)Maher et al. (2005); Cui et al. (2012a)
NPT1
 mRNA expressionFetal development (3%)20 daysIncreased progressivelyAdult age: 60 days. Strain: C57BL/6J (M). Methods: RNA-seqCui et al. (2012a)
  • bDNA, branched DNA signal amplification assay; CERP, cholesterol efflux regulatory protein; M, male; NR, not reported; RT-PCR, reverse-transcriptase polymerase chain reaction; RNA-seq, RNA-sequencing.