Serum alkaline phosphatase activity is regulated by a chromosomal region containing the alkaline phosphatase 2 gene (Akp2) in C57BL/6J and DBA/2J mice

Jennifer E. Foreman, David A. Blizard, Glenn Gerhard, Holly A. Mack, Dean H. Lang, Kathryn L. Van Nimwegen, George P. Vogler, Joseph T. Stout, Zakariya K. Shihabi, James W. Griffith, Joan M. Lakoski, Gerald E. McClearn, David J. Vandenbergh

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Abstract

Quantitative trait locus (QTL) analyses were conducted to identify chromosomal regions that contribute to variability in serum alkaline phosphatase (AP) enzyme activity in mice derived from the C57BL/6J (B6) and DBA/2J (D2) inbred strains. Serum AP was measured in 400 B6D2 F2 mice at 5 mo and 400 B6D2 F2 mice at 15 mo of age that were genotyped at 96 microsatellite markers, and in 19 BXD recombinant inbred (RI) strains at 5 mo of age. A QTL on the distal end of chromosome 4 was present in all sex- and age-specific analyses with a peak logarithm of odds (LOD) score of 20.36 at 58.51 cM. The Akp2 gene, which encodes the major serum AP isozyme, falls within this QTL region at 70.2 cM where the LOD score reached 13.2 (LOD significance level set at 4.3). Serum AP activity was directly related to the number of D2 alleles of a single nucleotide polymorphism in the 5′-flanking region of the Akp2 gene, although no strain-related differences in hepatic expression of Akp2 RNA were found. A variety of sequence polymorphisms in this chromosomal region could be responsible for the differences in serum AP activity; the Akp2 gene, however, with several known amino acid substitutions between protein sequences of the B6 and D2 strains, is a leading candidate.

Original languageEnglish (US)
Pages (from-to)295-303
Number of pages9
JournalPhysiological genomics
Volume23
Issue number3
DOIs
StatePublished - Oct 17 2005

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Inbred DBA Mouse
Alkaline Phosphatase
Serum
Genes
Quantitative Trait Loci
Chromosomes, Human, Pair 4
5' Flanking Region
Amino Acid Substitution
Inbred C57BL Mouse
Microsatellite Repeats
Isoenzymes
Single Nucleotide Polymorphism
Alleles
RNA
Liver

All Science Journal Classification (ASJC) codes

  • Physiology
  • Genetics

Cite this

Foreman, Jennifer E. ; Blizard, David A. ; Gerhard, Glenn ; Mack, Holly A. ; Lang, Dean H. ; Van Nimwegen, Kathryn L. ; Vogler, George P. ; Stout, Joseph T. ; Shihabi, Zakariya K. ; Griffith, James W. ; Lakoski, Joan M. ; McClearn, Gerald E. ; Vandenbergh, David J. / Serum alkaline phosphatase activity is regulated by a chromosomal region containing the alkaline phosphatase 2 gene (Akp2) in C57BL/6J and DBA/2J mice. In: Physiological genomics. 2005 ; Vol. 23, No. 3. pp. 295-303.
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title = "Serum alkaline phosphatase activity is regulated by a chromosomal region containing the alkaline phosphatase 2 gene (Akp2) in C57BL/6J and DBA/2J mice",
abstract = "Quantitative trait locus (QTL) analyses were conducted to identify chromosomal regions that contribute to variability in serum alkaline phosphatase (AP) enzyme activity in mice derived from the C57BL/6J (B6) and DBA/2J (D2) inbred strains. Serum AP was measured in 400 B6D2 F2 mice at 5 mo and 400 B6D2 F2 mice at 15 mo of age that were genotyped at 96 microsatellite markers, and in 19 BXD recombinant inbred (RI) strains at 5 mo of age. A QTL on the distal end of chromosome 4 was present in all sex- and age-specific analyses with a peak logarithm of odds (LOD) score of 20.36 at 58.51 cM. The Akp2 gene, which encodes the major serum AP isozyme, falls within this QTL region at 70.2 cM where the LOD score reached 13.2 (LOD significance level set at 4.3). Serum AP activity was directly related to the number of D2 alleles of a single nucleotide polymorphism in the 5′-flanking region of the Akp2 gene, although no strain-related differences in hepatic expression of Akp2 RNA were found. A variety of sequence polymorphisms in this chromosomal region could be responsible for the differences in serum AP activity; the Akp2 gene, however, with several known amino acid substitutions between protein sequences of the B6 and D2 strains, is a leading candidate.",
author = "Foreman, {Jennifer E.} and Blizard, {David A.} and Glenn Gerhard and Mack, {Holly A.} and Lang, {Dean H.} and {Van Nimwegen}, {Kathryn L.} and Vogler, {George P.} and Stout, {Joseph T.} and Shihabi, {Zakariya K.} and Griffith, {James W.} and Lakoski, {Joan M.} and McClearn, {Gerald E.} and Vandenbergh, {David J.}",
year = "2005",
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doi = "10.1152/physiolgenomics.00062.2005",
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Foreman, JE, Blizard, DA, Gerhard, G, Mack, HA, Lang, DH, Van Nimwegen, KL, Vogler, GP, Stout, JT, Shihabi, ZK, Griffith, JW, Lakoski, JM, McClearn, GE & Vandenbergh, DJ 2005, 'Serum alkaline phosphatase activity is regulated by a chromosomal region containing the alkaline phosphatase 2 gene (Akp2) in C57BL/6J and DBA/2J mice', Physiological genomics, vol. 23, no. 3, pp. 295-303. https://doi.org/10.1152/physiolgenomics.00062.2005

Serum alkaline phosphatase activity is regulated by a chromosomal region containing the alkaline phosphatase 2 gene (Akp2) in C57BL/6J and DBA/2J mice. / Foreman, Jennifer E.; Blizard, David A.; Gerhard, Glenn; Mack, Holly A.; Lang, Dean H.; Van Nimwegen, Kathryn L.; Vogler, George P.; Stout, Joseph T.; Shihabi, Zakariya K.; Griffith, James W.; Lakoski, Joan M.; McClearn, Gerald E.; Vandenbergh, David J.

In: Physiological genomics, Vol. 23, No. 3, 17.10.2005, p. 295-303.

Research output: Contribution to journalArticle

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T1 - Serum alkaline phosphatase activity is regulated by a chromosomal region containing the alkaline phosphatase 2 gene (Akp2) in C57BL/6J and DBA/2J mice

AU - Foreman, Jennifer E.

AU - Blizard, David A.

AU - Gerhard, Glenn

AU - Mack, Holly A.

AU - Lang, Dean H.

AU - Van Nimwegen, Kathryn L.

AU - Vogler, George P.

AU - Stout, Joseph T.

AU - Shihabi, Zakariya K.

AU - Griffith, James W.

AU - Lakoski, Joan M.

AU - McClearn, Gerald E.

AU - Vandenbergh, David J.

PY - 2005/10/17

Y1 - 2005/10/17

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