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

Siti W. Mohd-Zin, Nor Linda Abdullah, Aminah Abdullah, Nicholas D E Greene, Pike See Cheah, King Hwa Ling, Hadri Yusof, Ahmed I. Marwan, Sarah M. Williams, Kerri T. York, Azlina Ahmad-Annuar, Noraishah M. Abdul-Aziz, M. E. Cristescu

Research output: Contribution to journalArticle

2 Citations (Scopus)

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 Epha4rb-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 Epha4rb-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 Epha4rb-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.

Original languageEnglish
Pages (from-to)439-448
Number of pages10
JournalGenome / National Research Council Canada = Genome / Conseil national de recherches Canada
Volume59
Issue number7
DOIs
Publication statusPublished - 18 May 2016

Fingerprint

Eph Family Receptors
Ephrins
Mutation
EphA4 Receptor
Alleles
Phenotype
Frameshift Mutation
Proteins
Aptitude
Nonsense Codon
Locomotion
Gait
Base Pairing
Restriction Fragment Length Polymorphisms
Protein-Tyrosine Kinases
Embryonic Development
Exons
Protein Isoforms
Phosphotransferases
Extremities

Keywords

  • EphA4
  • Hopping gait
  • Knockout mouse
  • Rb-2J strain
  • Spontaneous mutation

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Biology
  • Genetics

Cite this

Identification of the genomic mutation in Epha4 rb-2J/rb-2J mice. / Mohd-Zin, Siti W.; Abdullah, Nor Linda; Abdullah, Aminah; Greene, Nicholas D E; Cheah, Pike See; Ling, King Hwa; Yusof, Hadri; Marwan, Ahmed I.; Williams, Sarah M.; York, Kerri T.; Ahmad-Annuar, Azlina; Abdul-Aziz, Noraishah M.; Cristescu, M. E.

In: Genome / National Research Council Canada = Genome / Conseil national de recherches Canada, Vol. 59, No. 7, 18.05.2016, p. 439-448.

Research output: Contribution to journalArticle

Mohd-Zin, SW, Abdullah, NL, Abdullah, A, Greene, NDE, Cheah, PS, Ling, KH, Yusof, H, Marwan, AI, Williams, SM, York, KT, Ahmad-Annuar, A, Abdul-Aziz, NM & Cristescu, ME 2016, 'Identification of the genomic mutation in Epha4 rb-2J/rb-2J mice', Genome / National Research Council Canada = Genome / Conseil national de recherches Canada, vol. 59, no. 7, pp. 439-448. https://doi.org/10.1139/gen-2015-0142
Mohd-Zin, Siti W. ; Abdullah, Nor Linda ; Abdullah, Aminah ; Greene, Nicholas D E ; Cheah, Pike See ; Ling, King Hwa ; Yusof, Hadri ; Marwan, Ahmed I. ; Williams, Sarah M. ; York, Kerri T. ; Ahmad-Annuar, Azlina ; Abdul-Aziz, Noraishah M. ; Cristescu, M. E. / Identification of the genomic mutation in Epha4 rb-2J/rb-2J mice. In: Genome / National Research Council Canada = Genome / Conseil national de recherches Canada. 2016 ; Vol. 59, No. 7. pp. 439-448.
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AU - Abdullah, Nor Linda

AU - Abdullah, Aminah

AU - Greene, Nicholas D E

AU - Cheah, Pike See

AU - Ling, King Hwa

AU - Yusof, Hadri

AU - Marwan, Ahmed I.

AU - Williams, Sarah M.

AU - York, Kerri T.

AU - Ahmad-Annuar, Azlina

AU - Abdul-Aziz, Noraishah M.

AU - Cristescu, M. E.

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N2 - 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 Epha4rb-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 Epha4rb-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 Epha4rb-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.

AB - 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 Epha4rb-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 Epha4rb-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 Epha4rb-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.

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