No evidence of non-homologous insertions in mouse model of MDD created by replacement of homologous mouse DNA sequence with pathogenic 6-base human CREB1 promoter sequence

• Published in: American journal of medical genetics. Part B, Neuropsychiatric genetics Neuropsychiatric genetics, 2012-01, Vol.159B (1), p.1-4
• Main Authors: Zubenko, George S., Hughes III, Hugh B.
• Format: Article
• Language: English
• Subjects: animal model; Animals; Base Pairing - genetics; Base Sequence; Cyclic AMP Response Element-Binding Protein - genetics; Deoxyribonucleic acid; Depressive Disorder, Major - genetics; Disease Models, Animal; DNA; Electrophoresis, Agar Gel; Etiology; Gene Targeting; Genetic Vectors - genetics; Genetics; Genomes; Homologous recombination; Humans; major depressive disorder; Mental depression; Mice; mouse; Mutagenesis, Insertional - genetics; Nucleotide sequence; Polymerase Chain Reaction; Promoter Regions, Genetic - genetics; Rodents; Sequence Homology
• ISSN: 1552-4841; 1552-485X
• DOI: 10.1002/ajmg.b.32006

We have recently reported the creation and initial characterization of the first etiology‐based recombinant mouse model of major depressive disorder (MDD). This was achieved by replacing the corresponding mouse DNA sequence with a 6‐base DNA sequence from the human CREB1 promoter that is associated with the development of MDD in families identified by probands with recurrent, early‐onset MDD. The current study explored whether the desired homologous recombination event at the mouse Creb1 gene that resulted in the creation of the mouse model was also accompanied by insertions of the targeting vector at unintended non‐homologous locations in the mouse genome. No evidence of insertions of targeting vector sequence was observed at regions other than the mouse Creb1 gene. © 2011 Wiley Periodicals, Inc.