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

• Published in: Physiological genomics 2005-11, Vol.23 (3), p.295-303
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Alkaline Phosphatase - blood; Alkaline Phosphatase - genetics; Animals; Base Sequence; Chromosome Mapping; Crosses, Genetic; DNA Primers; Female; Genotype; Male; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; Quantitative Trait Loci; Y Chromosome
• ISSN: 1094-8341; 1531-2267
• DOI: 10.1152/physiolgenomics.00062.2005

1 Center for Developmental and Health Genetics 2 Intercollege Program in Genetics 3 Department of Biobehavioral Health 4 Department of Kinesiology, The Pennsylvania State University, University Park, Pennsylvania 5 Weis Center for Research, Geisinger Clinic, Danville, Pennsylvania 6 Department of Pathology, Wake Forest University Medical Center, Winston-Salem, North Carolina 7 Department of Comparative Medicine, College of Medicine, The Pennsylvania State University, Hershey, Pennsylvania 8 Department of Pharmacology, University of Pittsburgh, Pittsburgh, Pennsylvania 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 F 2 mice at 5 mo and 400 B6D2 F 2 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. blood; aging; liver enzymes; bone enzymes; quantitative trait locus