These mir-290-295-/- mice exhibit an incomplete homozygous lethal phenotype. Surviving homozygous females are sterile, with reduced oocyte number. Embryonic primordial germ cell migration is mislocalized.
Rudolf Jaenisch, Whitehead Institute, Massachusetts Institute of Technology
Approximately 75% of homozygotes die before birth of unknown causes. The surviving homozygous females are sterile. Mice that are heterozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. No gene product (mRNA) is detected by Northern blot or real-time RT-PCR analysis of homozygous knockout ES cells lines produced from mutant mice. Homozygous embryos exhibit development delays as early as embryonic day 8.5, and loss of homozygous embryos occurs E11.5 to E18.5. Approximately 16% of homozygous embryos, at E10.5 or younger, are partially or completely outside the yolk sac. Embryonic primordial germ cell migration is mislocalized. A reduced number of gonocytes/germ cells in homozygotes is detectable as early as E11.5. Homozygous adult females have smaller size ovaries when compared to wildtype littermates. Ovaries from 5 to 8 week old homozygotes have few follicles, and in ovaries from homozygous females 10 weeks of age or older, no follicles are observed. Although, homozygous males are fertile, testes from homozygous males have some empty seminiferous tubules.
A targeting vector containing a PGK-NEO cassette was used to disrupt 2 kb of sequence encoding both genes. The construct was electroporated into (C57BL/6 x 129S4/SvJae)F1 derived V6.5 embryonic stem (ES) cells. Correctly targeted ES cells were injected into B6D2F2 blastocysts. Male germline transmission of the mutation was confirmed. The mice were maintained on a mixed B6;129S4 background. Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the colony.
|Allele Name||targeted mutation 1, Rudolf Jaenisch|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||mir-290-295-; xmiR290 cluster -|
|Gene Symbol and Name||Mirc5, microRNA cluster 5, including Mir290a through Mir295|
|Strain of Origin||(C57BL/6 x 129S4/SvJae)F1|
|Molecular Note||The entire 2 kb cluster including Mir290, Mir291a, Mir292, Mir291b, Mir293, Mir294, and Mir295 was replaced with a pgk-neo cassette via homologous recombination. RT-PCR confirmed the absence of mature micro RNAs in homozygous ES cells.|
|Mutations Made By|| |
Lea Medeiros, Whitehead Institute
When maintaining a live colony, these mice can be bred as heterozygotes. Approximately 75% of homozygotes die before birth of unknown causes. The surviving homozygous females are sterile.
When using the B6;129S4-Mirc5tm1Jae/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #017337 in your Materials and Methods section.