Localization, transmission, spontaneous mutations, and variation of function of the Dpp4 (Dipeptidyl-peptidase IV; CD26) gene in rats.
Dipeptidyl-peptidase IV (DPPIV) is involved in endocrine and immune functions via cleavage of regulatory peptides with a N-terminal proline or alanine such as incretins, neuropeptide Y, or several chemokines. So far no systematic investigations on the localization and transmission of the Dpp4 gene or the natural variations of DPPIV-like enzymatic function in different rat strains have been conducted. Here we mapped the Dpp4 gene to rat chromosome 3 and describe a semi-dominant mode of inheritance for Dpp4 in a mutant F344/DuCrj(DPPIV-) rat substrain lacking endogenous DPPIV-like activity. This mutant F344/DuCrj(DPPIV-) rat substrain constantly exhibits a nearly complete lack of DPPIV-like enzymatic activity, while segregation of DPPIV-like enzymatic activity was observed in another DPPIV-negative F344/Crl(Ger/DPPIV-) rat substrain. Screening of 12 different inbred laboratory rat strains revealed dramatic differences in DPPIV-like activity ranging from 11 mU/microl (LEW/Ztm rats) to 40 mU/microl (BN/Ztm and DA/Ztm rats). A lack of DPPIV-like activity in F344 rats was associated with an improved glucose tolerance and blunted natural killer cell function, which indicates the pleiotropic functional role of DPPIV in vivo. Overall, the variations in DPPIV-like enzymatic activity probably represent important confounding factors in studies using rat models for research on regulatory peptides.
Karl
Tim
T
Department of Functional and Applied Anatomy, Hannover Medical School, OE 4120, Carl-Neuberg-Str. 1, 30623, Hannover, Germany.
Chwalisz
Wojciech T
WT
Wedekind
Dirk
D
Hedrich
Hans J
HJ
Hoffmann
Torsten
T
Jacobs
Roland
R
Pabst
Reinhard
R
von Hörsten
Stephan
S
D000818:Animals; D001786:Blood Glucose / Q000235:genetics / Q000378:metabolism; D020090:Chromosome Segregation; D002875:Chromosomes / Q000235:genetics; D003602:Cytotoxicity, Immunologic; D018819:Dipeptidyl Peptidase 4 / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D005799:Genes, Dominant; D014644:Genetic Variation; D005951:Glucose Tolerance Test; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism*; D008297:Male; D009154:Mutation / Q000235:genetics*; D010446:Peptide Fragments / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D011922:Rats, Mutant Strains / Q000235:genetics*
D001786:Blood Glucose; D010446:Peptide Fragments; D018819:Dipeptidyl Peptidase 4