Cre 발현유도 시스템을 이용한 유전자 기능 연구 = Functional Study of Gene using Inducible Cre System

다국어 초록 (Multilingual Abstract)

Gene manipulation by disrupting important genes using homologous recombination in mammals has provided important insights into their function and development with regard to disease. However, many questions related to the genetic pathways that regulate cellular differentiation and function remain to be clarified. In particular, analysis of genetic pathways that control embryonic skeletal development is often hindered by the disruption of critical genes that function in early embryogenesis, thereby leading to embryonic or perinatal death and thus preventing study of the role of these genes in skeletal development and physiology postnatally. To overcome this problem gene-targeting methods, using site- and time-specific recombination based methods with the Cre/loxP system, have been used to delete particular genes in specific tissues and stages during development. Thus, the generation and characterization of transgenic mice expressing Cre recombinase, under the control of a tissue-specific and stage-specific promoter, has become prerequisite for study of the physiology and homeostasis of specific tissues during a specific time frame. In this report, we introduce the principles and methods of site-specific and time-specific recombination using the Cre/loxP and inducible Cre system, and discuss the potential applications for applying this system to the study of the development and physiology of the skeletal system. (J Kor Endocrinol Soc 21:364~369, 2006)

참고문헌 (Reference)

1 "Two distinct osteoblast-specific cis-acting elements control expression of a mouse osteocalcin gene" 15 : 1858-1869, 1995

2 "Transgenic mice expressing a ligand-inducible cre recombinase in osteoblasts and odontoblasts:a new tool to examine physiology and disease of postnatal bone and tooth" 165 : 1875-1882, 2004

3 "The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation" 108 : 17-29, 2002

4 "Temporally-controlled site-specific mutagenesis in the basal layer of the epidermis: comparison of the recombinase activity of the tamoxifen-inducible Cre-ER(T) and Cre-ER(T2) recombinases." 27 : 4324-4327, 1999

5 "Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts" 89 : 755-764, 1997

6 "Tamoxifen-inducible glia-specific Cre mice for somatic mutagenesis in oligodendrocytes and Schwann cells" 22 : 430-440, 2003

7 "Subnuclear targeting of Runx/Cbfa/AML factors is essential for tissue-specific differentiation during embryonic development" 98 : 8650-8655, 2001

8 "Separate cis-acting DNA elements of the mouse pro-alpha-1(I)collagen promoter direct expression of reporter genes to different type I collagen-producing cells in transgenic mice" 129 : 1421-1432, 1995

9 "Regulation of Cre recombinase activity by mutated estrogen receptor ligand-binding domains" 237 : 752-757, 1997

10 "Recombination between loxP sites" 467-486, 1981

11 "Mouse alpha-1(I)-collagen promoter is the best known promoter to drive efficient Cre recombinase expression in osteoblast" 224 : 245-251, 2002

12 "Generalized lacZ expression with the ROSA26 Cre reporter strain" 21 : 70-71, 1999

13 "Conditional gene targeting" 98 : 600-603, 1996

14 "Conditional gene knockout using Cre recombinase" 136 : 477-485, 2000

15 "Col1a1-GFP transgene expression in developing incisors" 43 : 216-219, 2002

16 "Cbfa1, a candidate gene for cleidocranial dysplasia syndrome, is essential for osteoblast differentiation and bone development." 89 : 765-771, 1997