title: Generation of mice with a novel conditional null allele of the Sox9 gene.
abstract: Sox9 is expressed in multiple tissues during mouse development and adulthood. Mutations in the Sox9 gene or changes in expression levels can be attributed to many congenital diseases. Heterozygous loss-of-function mutations in the human SOX9 gene cause Campomelic dysplasia, a semi-lethal skeletal malformation syndrome. Disruption of Sox9 by conventional gene targeting leads to perinatal lethality in heterozygous mice, hence hampering the feasibility to obtain the homozygous Sox9 null mice for in vivo functional studies. In this study, we generated a conditional allele of Sox9 (Sox9 ( tm4.Tlu )) by flanking exon 1 with loxP sites. Homozygous mice for the Sox9 ( tm4.Tlu ) allele (Sox9 ( flox/flox )) are viable, fertile and indistinguishable from wildtype (WT) mice, indicating that the Sox9 ( tm4.Tlu ) allele is a fully functional Sox9 allele. Furthermore, we demonstrated that Cre-mediated recombination using a Col2a1-Cre line resulted in specific ablation of Sox9 activity in cartilage tissues.
authors.affiliation: Stem Cell and Developmental Biology, Genome Institute of Singapore, 60 Biopolis Street, Singapore. yaps@gis.a-star.edu.sg
authors.forename: Sook Peng
authors.initials: SP
authors.lastname: Yap
authors.forename: Xing
authors.initials: X
authors.lastname: Xing
authors.forename: Petra
authors.initials: P
authors.lastname: Kraus
authors.forename: V
authors.initials: V
authors.lastname: Sivakamasundari
authors.forename: Hsiao Yun
authors.initials: HY
authors.lastname: Chan
authors.forename: Thomas
authors.initials: T
authors.lastname: Lufkin
mesh_terms: D000483:Alleles; D000818:Animals; D003001:Cloning, Molecular; D024043:Collagen Type II / Q000235:genetics; D004622:Embryo, Mammalian; D005552:Forelimb / Q000196:embryology / Q000473:pathology; D018628:Gene Dosage; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D055786:Gene Knockout Techniques / Q000379:methods*; D018390:Gene Targeting; D006651:Histocytochemistry; D019426:Integrases / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D008957:Models, Genetic; D041641:Musculoskeletal Development / Q000235:genetics; D055758:SOX9 Transcription Factor / Q000235:genetics*; D013131:Spine / Q000196:embryology / Q000473:pathology
chemical_list: C447413:Col2a1 protein, mouse; D024043:Collagen Type II; D055758:SOX9 Transcription Factor; C527933:Sox9 protein, mouse; C045073:Cre recombinase; D019426:Integrases