title: Targeted disruption of fad24, a regulator of adipogenesis, causes pre-implantation embryonic lethality due to the growth defect at the blastocyst stage.
abstract: In previous studies, we identified a novel gene, factor for adipocyte differentiation 24 (fad24), which plays an important role during the early stages of adipogenesis in mouse 3T3-L1 cells. Moreover, overexpression of fad24 increased the number of smaller adipocytes in white adipose tissue and improved glucose metabolic activity in mice, thus indicating that fad24 functions as a regulator of adipogenesis in vivo. However, the physiological roles of fad24 in vivo are largely unknown. In this study, we attempted to generate fad24-deficient mice by gene targeting. No fad24-null mutants were recovered after embryonic day 9.5 (E9.5). Although fad24-null embryos were detected in an expected Mendelian ratio of genotypes at E3.5, none of the homozygous mutants developed into blastocysts. In vitro culture experiments revealed that fad24-null embryos develop normally to the morula stage but acquire growth defects during subsequent stages. The number of nuclei decreased in fad24-deficient morulae compared with that in wild-type ones. These results strongly suggested that fad24 is essential for pre-implantation in embryonic development, particularly for the progression to the blastocyst stage.
authors.affiliation: Department of Molecular Biology, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi 467-8603, Japan.
authors.forename: Natsuki
authors.initials: N
authors.lastname: Ochiai
authors.forename: Makoto
authors.initials: M
authors.lastname: Nishizuka
authors.forename: Tomomi
authors.initials: T
authors.lastname: Miyamoto
authors.forename: Ichiro
authors.initials: I
authors.lastname: Miyoshi
authors.forename: Masahito
authors.initials: M
authors.lastname: Ikawa
authors.forename: Shigehiro
authors.initials: S
authors.lastname: Osada
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Imagawa
mesh_terms: D041721:3T3-L1 Cells; D050156:Adipogenesis; D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics* / Q000502:physiology*; D001755:Blastocyst / Q000166:cytology*; D018797:Cell Cycle Proteins; D003433:Crosses, Genetic; D053595:Embryonic Stem Cells / Q000166:cytology; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D005947:Glucose / Q000378:metabolism; D006579:Heterozygote; D006720:Homozygote; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009028:Morula / Q000378:metabolism; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics* / Q000502:physiology*; D013997:Time Factors
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; D018797:Cell Cycle Proteins; C502215:Noc3l protein, mouse; D009687:Nuclear Proteins; D005947:Glucose
keywords: 4′,6-diamidino-2-phenylindole; Adipogenesis; Blastocyst; DAPI; E; Embryonic development; Embryonic lethality; HBO1; IVF; Morula; Neo; Noc; PBS; PCR; TK; embryonic day; factor for adipocyte differentiation; fad; fad24; histone acetyltransferase binding to ORC1; in vitro fertilization; neomycin resistance; nucleolar complex-associated protein; phosphate buffered saline; polymerase chain reaction; thymidine kinase