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Generation of a Magoh conditional allele in mice.
Genesis 2014; 52(8):752-8G

Abstract

Magoh encodes a core component of the exon junction complex (EJC), which binds mRNA and regulates mRNA metabolism. Magoh is highly expressed in proliferative tissues during development. EJC components have been implicated in several developmental disorders including TAR syndrome, Richieri-Costa-Pereira syndrome, and intellectual disability. Existing germline null Magoh mice are embryonic lethal as homozygotes and perinatal lethal as heterozygotes, precluding detailed analysis of embryonic and postnatal functions. Here, we report the generation of a new genetic tool to dissect temporal and tissue-specific roles for Magoh in development and adult homeostasis. This Magoh conditional allele has two loxP sites flanking the second exon. Ubiquitous Cre-mediated deletion of the floxed allele in a heterozygous mouse (Magoh(del/+)) causes 50% reduction of both Magoh mRNA and protein. Magoh(del/+) mice exhibit both microcephaly and hypopigmentation, thus phenocopying germline haploinsufficient Magoh mice. Using Emx1-Cre, we further show that conditional Magoh deletion in neural progenitors during embryonic development also causes microcephaly. We anticipate this novel conditional allele will be a valuable tool for assessing tissue-specific roles for Magoh in mammalian development and postnatal processes.

Authors+Show Affiliations

Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

24771530

Citation

McMahon, John J., et al. "Generation of a Magoh Conditional Allele in Mice." Genesis (New York, N.Y. : 2000), vol. 52, no. 8, 2014, pp. 752-8.
McMahon JJ, Shi L, Silver DL. Generation of a Magoh conditional allele in mice. Genesis. 2014;52(8):752-8.
McMahon, J. J., Shi, L., & Silver, D. L. (2014). Generation of a Magoh conditional allele in mice. Genesis (New York, N.Y. : 2000), 52(8), pp. 752-8. doi:10.1002/dvg.22788.
McMahon JJ, Shi L, Silver DL. Generation of a Magoh Conditional Allele in Mice. Genesis. 2014;52(8):752-8. PubMed PMID: 24771530.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Generation of a Magoh conditional allele in mice. AU - McMahon,John J, AU - Shi,Lei, AU - Silver,Debra L, Y1 - 2014/05/09/ PY - 2014/03/18/received PY - 2014/04/22/revised PY - 2014/04/24/accepted PY - 2014/4/29/entrez PY - 2014/4/29/pubmed PY - 2015/3/31/medline KW - Magoh KW - conditional allele KW - cre KW - exon junction complex KW - lox KW - microcephaly SP - 752 EP - 8 JF - Genesis (New York, N.Y. : 2000) JO - Genesis VL - 52 IS - 8 N2 - Magoh encodes a core component of the exon junction complex (EJC), which binds mRNA and regulates mRNA metabolism. Magoh is highly expressed in proliferative tissues during development. EJC components have been implicated in several developmental disorders including TAR syndrome, Richieri-Costa-Pereira syndrome, and intellectual disability. Existing germline null Magoh mice are embryonic lethal as homozygotes and perinatal lethal as heterozygotes, precluding detailed analysis of embryonic and postnatal functions. Here, we report the generation of a new genetic tool to dissect temporal and tissue-specific roles for Magoh in development and adult homeostasis. This Magoh conditional allele has two loxP sites flanking the second exon. Ubiquitous Cre-mediated deletion of the floxed allele in a heterozygous mouse (Magoh(del/+)) causes 50% reduction of both Magoh mRNA and protein. Magoh(del/+) mice exhibit both microcephaly and hypopigmentation, thus phenocopying germline haploinsufficient Magoh mice. Using Emx1-Cre, we further show that conditional Magoh deletion in neural progenitors during embryonic development also causes microcephaly. We anticipate this novel conditional allele will be a valuable tool for assessing tissue-specific roles for Magoh in mammalian development and postnatal processes. SN - 1526-968X UR - https://www.unboundmedicine.com/medline/citation/24771530/Generation_of_a_Magoh_conditional_allele_in_mice_ L2 - https://doi.org/10.1002/dvg.22788 DB - PRIME DP - Unbound Medicine ER -