Map2k1^tm2.1Chrn
Targeted Allele Detail

Summary

• Symbol: Map2k1^tm2.1Chrn
• Name: mitogen-activated protein kinase kinase 1; targeted mutation 2.1, M Jean Charron
• MGI ID: MGI:6157680
• Synonyms: Mek1^Y130C
• Gene: Map2k1 Location: Chr9:64093066-64160887 bp, - strand Genetic Position: Chr9, 34.55 cM
• Alliance: Map2k1^tm2.1Chrn page

Mutation origin

• Germline Transmission: Earliest citation of germline transmission: J:261678
• Parent Cell Line: WW6 (ES Cell)
• Strain of Origin: STOCK 129/Sv and C57BL/6J and SJL

Mutation description

• Allele Type: Targeted (Humanized sequence)
• Mutations: Duplication, Insertion, Single point mutation
• Mutation details: The gene was targeted to reproduce the most common human mutation associated with cardio-facial-cutaneous (CFC) syndrome by creating an A-to-G transition in exon 3 at the base corresponding to nucleotide position 389 of the cDNA, resulting in replacement of tyrosine by cysteine at amino acid position 130 of the protein (Y130C). A loxP-flanked neomycin selection cassette was introduced and subsequently deleted by Cre recombinase, leaving a single loxP site in intron 2. Sequence analysis revealed a 61.4-kb intragenic duplication beginning 5.6 kb upstream of the transcription initiation site and extending into the fifth intron, with a single break junction between intron 5 of the 5' copy and the upstream sequence of the 3' copy suggesting it arose through unequal crossing over. Southern blot analysis using a restriction endonuclease that cuts within the intron 2 loxP sequence showed that the Y130C point mutation resides in the 5' copy.

  Total Map2k1 mRNA abundance in kidneys, lungs and thymi of mice heterozygous for this and a null mutation (Map2k1^tm1Chrn) was shown via qRT-PCR to be about half that in wild-type (Map2k1^+/+) tissues; sequence analysis of the qRT-PCR products revealed the presence of both Y130C mutant and wild-type transcripts in the compound heterozygotes. Similarly, immunoblot analyses demonstrated total MAP2K1 protein levels in both Map2k1^tm2.1Chrn/ Map2k1^tm1Chrn (Mek1^Y130C/-) and Map2k1⁺/ Map2k1^tm1Chrn (Mek1^+/-) tissues ~50% of wild-type (Mek^+/+) levels. (J:261678)

Disease models

Expression

In Structures Affected by this Mutation:

1 anatomical structure(s)

Find Mice (IMSR)

• Mouse strains and cell lines available from the International Mouse Strain Resource (IMSR)
• Carrying this Mutation: Mouse Strains: 1 strain available Cell Lines: 0 lines available
• Carrying any Map2k1 Mutation: 94 strains or lines available

References

• Original: J:261678 Aoidi R, et al., Mek1(Y130C) mice recapitulate aspects of human cardio-facio-cutaneous syndrome. Dis Model Mech. 2018 Mar 13;11(3):dmm031278
• All: 1 reference(s)