title: Identification of the genomic mutation in Epha4(rb-2J/rb-2J) mice.
abstract: The EphA4 receptor tyrosine kinase is involved in numerous cell-signalling activities during embryonic development. EphA4 has the ability to bind to both types of ephrin ligands, the ephrinAs and ephrinBs. The C57BL/6J-Epha4rb-2J/GrsrJ strain, denoted Epha4(rb-2J/rb-2J), is a spontaneous mouse mutant that arose at The Jackson Laboratory. These mutants exhibited a synchronous hind limb locomotion defect or "hopping gait" phenotype, which is also characteristic of EphA4 null mice. Genetic complementation experiments suggested that Epha4(rb-2J) corresponds to an allele of EphA4, but details of the genomic defect in this mouse mutant are currently unavailable. We found a single base-pair deletion in exon 9 resulting in a frame shift mutation that subsequently resulted in a premature stop codon. Analysis of the predicted structure of the truncated protein suggests that both the kinase and sterile α motif (SAM) domains are absent. Definitive determination of genotype is needed for experimental studies of mice carrying the Epha4(rb-2J) allele, and we have also developed a method to ease detection of the mutation through RFLP. Eph-ephrin family members are reportedly expressed as numerous isoforms. Hence, delineation of the specific mutation in EphA4 in this strain is important for further functional studies, such as protein-protein interactions, immunostaining and gene compensatory studies, investigating the mechanism underlying the effects of altered function of Eph family of receptor tyrosine kinases on phenotype.
authors.affiliation: a Department of Parasitology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Siti W
authors.initials: SW
authors.lastname: Mohd-Zin
authors.affiliation: a Department of Parasitology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Nor-Linda
authors.initials: NL
authors.lastname: Abdullah
authors.affiliation: b School of Chemical Science and Food Technology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, Bangi, 43600 Selangor, Malaysia.
authors.forename: Aminah
authors.initials: A
authors.lastname: Abdullah
authors.affiliation: c Birth Defects Research Centre, Developmental Biology and Cancer Programme, Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, UK.
authors.forename: Nicholas D E
authors.initials: ND
authors.lastname: Greene
authors.affiliation: d Genetics and Regenerative Medicine Research Centre, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor DE, Malaysia.
authors.forename: Pike-See
authors.initials: PS
authors.lastname: Cheah
authors.affiliation: d Genetics and Regenerative Medicine Research Centre, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor DE, Malaysia.|e Department of Obstetrics and Gynaecology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor DE, Malaysia.
authors.forename: King-Hwa
authors.initials: KH
authors.lastname: Ling
authors.affiliation: d Genetics and Regenerative Medicine Research Centre, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor DE, Malaysia.
authors.forename: Hadri
authors.initials: H
authors.lastname: Yusof
authors.affiliation: f Department of Surgery, University of Colorado Denver, Anschutz Medical Campus, 12700 E 17th Ave., Aurora, CO 80045, USA.
authors.forename: Ahmed I
authors.initials: AI
authors.lastname: Marwan
authors.affiliation: f Department of Surgery, University of Colorado Denver, Anschutz Medical Campus, 12700 E 17th Ave., Aurora, CO 80045, USA.
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Williams
authors.affiliation: f Department of Surgery, University of Colorado Denver, Anschutz Medical Campus, 12700 E 17th Ave., Aurora, CO 80045, USA.
authors.forename: Kerri T
authors.initials: KT
authors.lastname: York
authors.affiliation: g Department of Biomedical Science, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Azlina
authors.initials: A
authors.lastname: Ahmad-Annuar
authors.affiliation: a Department of Parasitology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Noraishah M
authors.initials: NM
authors.lastname: Abdul-Aziz
mesh_terms: D000483:Alleles; D000818:Animals; D018388:Codon, Terminator; D005091:Exons; D005260:Female; D015870:Gene Expression; D023281:Genomics; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016133:Polymerase Chain Reaction / Q000379:methods; D012150:Polymorphism, Restriction Fragment Length; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D036122:Receptor, EphA4 / Q000235:genetics*; D017384:Sequence Deletion; D015398:Signal Transduction; D000071682:Sterile Alpha Motif
chemical_list: D018388:Codon, Terminator; D012313:RNA; D036122:Receptor, EphA4
keywords: EphA4; démarche sautillante; hopping gait; knockout mouse; mutation spontanée; rb-2J strain; souche rb-2J; souris knock-out; spontaneous mutation