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Genome. 2016 Jul;59(7):439-48. doi: 10.1139/gen-2015-0142.

Identification of the genomic mutation in Epha4(rb-2J/rb-2J) mice.

Author information

1
a Department of Parasitology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
2
b School of Chemical Science and Food Technology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, Bangi, 43600 Selangor, Malaysia.
3
c Birth Defects Research Centre, Developmental Biology and Cancer Programme, Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, UK.
4
d Genetics and Regenerative Medicine Research Centre, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor DE, Malaysia.
5
e Department of Obstetrics and Gynaecology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor DE, Malaysia.
6
f Department of Surgery, University of Colorado Denver, Anschutz Medical Campus, 12700 E 17th Ave., Aurora, CO 80045, USA.
7
g Department of Biomedical Science, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.

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.

KEYWORDS:

EphA4; démarche sautillante; hopping gait; knockout mouse; mutation spontanée; rb-2J strain; souche rb-2J; souris knock-out; spontaneous mutation

PMID:
27373307
DOI:
10.1139/gen-2015-0142
[Indexed for MEDLINE]

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