Ptf1a Promoter-Driven Cre Expression During Spermatogenesis Causes Germline Recombination

Objectives: Two independently developed Ptf1a-Cre mouse lines, Ptf1a(tm1(cre)Hnak) and Ptf1a(tm1(Cre)Cvw), are widely used in pancreatic research. Recently, Ptf1a(tm1(cre)Hnak) line was reported to transmit unwanted paternal recombination. We aimed to investigate whether this exists in the Ptf1a(tm1(Cre)Cvw) line. Methods: Ptf1a(tm1(Cre)Cvw) mice were crossed with R26-LSL-LacZ reporter mice. DNA recombination and gene expression were examined by recombination-specific polymerase chain reaction, reverse transcription-polymerase chain reaction, and X-Gal staining. Results: R26 locus recombination was detected in the pancreas as well as the testes and sperm of the double transgenic mice. Positive ptf1a mRNA expression from testes revealed that there was endogenous Ptf1a promoter activity in this extrapancreatic tissue. Of the 15 progenies that inherited LacZ from the male double transgenic mice, 4 (26.7%) were positive for complete whole-body recombination. The presence of recombination in R26 only mice suggested that the recombination occurred before meiosis. Conclusions: Paternal germline recombination exists in the Ptf1a(tm1(Cre)Cvw) mouse line. Ptf1a promoter-driven Cre expression during spermatogenesis before meiosis is the cause of germline recombination. Therefore, when male Ptf1a-Cre mice are used in compound mice breeding, it is necessary to genotype not only floxed alleles but also recombined alleles to examine unwanted recombinations.