This miR-17~92Δ17 knock-out strain exhibits skeletal defects and is useful in studies related to Feingold Syndrome and the Mirc1 microRNA cluster.
Andrea Ventura, Memorial Sloan Kettering Cancer Center
The polycistronic Mirc1, microRNA cluster, or miR-17~92, consists of 6 members: Mir17, microRNA 17; Mir18, microRNA 18; Mir19a, microRNA 19a; Mir20a, microRNA 20a; Mir19b-1, microRNA 19b-1; and Mir92-1, microRNA 92-1. The region of nucleotides 2–7 from the mature miRNA 5´-end is called the miRNA seed sequence, which is essential for target recognition and binding to mRNA. The same seed sequence is often shared amongst miRNAs within the same family.
These miR-17~92Δ17 mice have the miR-17 single seed family (Mir17 and Mir20a) knocked out of the Mirc1, microRNA cluster.
No Mir17 or Mir20a miRNAs are detected by RT-qPCR and small RNA sequencing analysis of tail tissue from homozygotes. Mice that are homozygous for the targeted mutation are viable and fertile on the B6;129 background. Mendelian frequency for homozygotes on the C57BL/6J background is lower than expected (7%). Homozygotes (N7 on the C57BL/6 background) exhibit fused proximal carpal bones, vertebral fusions, and fully penetrant homeotic transformations of one or more vertebrae. Heterozygotes and homozygotes (N7 on the C57BL/6 background) exhibit shortened fifth mesophalanx. Pre-B-cell number is reduced and ossification is delayed in homozygotes on the B6;129 background. Homozygotes are smaller than wildtype controls. The severity of the phenotype (including perinatal lethality) in homozygotes increases when the mice are backcrossed to C57BL/6. Levels of Mir18a (miR-18a) miRNA are reduced in homozygotes.
This strain is part of a miR-17~92 (Mirc1, microRNA cluster 1, including Mir17 through Mir92-1) allelic series:
(Stock No. 027317), (Stock No. 027318),
(Stock No. 027319), (Stock No. 027320), (Stock No. 027321), (Stock No. 027322).
|Allele Name||targeted mutation 1.1, Andrea Ventura|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Mirc1, microRNA cluster 1, including Mir17 through Mir92-1|
|Strain of Origin||(C57BL/6 x 129S4/SvJae)F1|
|Molecular Note||The Mir17 and Mir20a genes were replaced by a FRT-flanked neomycin cassette. Flp-mediated recombination removed the FRT-flanked neo cassette.|
When maintaining a live colony, heterozygous mice may be bred together, to wildtype siblings, or to C57BL/6J inbred mice (Stock No. 000664). The severity of the phenotype (including perinatal lethality) in homozygotes increases when the mice are backcrossed to C57BL/6.
When using the B6.Cg-Mirc1tm1.1Aven/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #027317 in your Materials and Methods section.