These black mice…

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A C57 black mouse

A "C57 black mouse"

 All researchers, students or technicians, sooner or later, come across the same questions, namely: “-which exact strain are “these black mice” we have in the animal house?”, “- I’ve been told they were “C57 black” but, I realised there are MANY similar mouse strains under this generic name.”  Indeed, there are several “C57black”-related mouse strains, that are NOT genetically identical and, therefore, the exact knowledge and recognisition of the appropriate mouse strain you are working with (i.e. or the mouse strain from which the ES cell that you’re using was originally derived)  is crucial for the success (or fiasco) of the corresponding scientific project. This point was nicely addressed by Johannes Wilbertz, ISTT Vice-President, at the last TT2008 meeting, held in Toronto. Here, I’d like to briefly summarise the most common “C57 black” mice and provide the corresponding links for interested readers, to explore additional information.

C57black is the “common” name (argot) of the “C57BL/6″ mouse strain, that can be purchased and obtained from different animal providers which originally obtained their starting mouse colonies from distinct stocks ,or even from the same stock but in different times, thus resulting (by genetic drift) in genetically divergent mouse strains. Considering four of the major mouse providers (The Jackson Laboratory, Charles River, Harlan and Taconic) these are the different C57BL/6 mice they sell and distribute.

THE JACKSON LABORATORY

C57BL/6J    These are the original “/J” mice, JAX Mouse strain #000664.

C57BL/6NJ   These are the “original /N” mice, who came from Jax to NIH, where they were bred and established and eventually returned to Jackson Lab, constituting the JAX Mouse strain #005304.

In addition, there are other C57BL/6 – related mouse strains available from Jackson, including the albino C57BL/6J mice, called B6(Cg)-Tyr<c-2j>/J mice or JAX Mouse strain #000058.

CHARLES RIVER

C57BL/6J   (available outside US) These are in principal “equivalent” to the original C57BL/6J mice from The Jackson Laboratory, transferred to France in 1981 and to UK in 2004 and bred according to JAX protocols.

C57BL/6NCrl   These originated in The Jackson Laboratory, were transferred to NIH in 1951 and then to Charles River in 1974.

Thanks to a comment received from Kate Pritchett, from Charles River, it must be noted that, for UK-customers, there is currently a third additional C57BL/6 strain available from this animal provider, identified as “C57BL/6JCrl”, that will be eventually discontinued, due to the contract agreements in place between Charles River and The Jackson Laboratory.

HARLAN

C57BL/6JOlaHsd   (available in Europe) These were originated in The Jackson Laboratory and were transferred to OLAC in 1983.

C57BL/6JRccHsd   (available in Europe) These were originated in The Jackson Laboratory and were transferred through RCC in 1973.

C57BL/6NHsd   These were originated in The Jackson Laboratory and then were transferred to NIH in 1974 and from there to Harlan.

TACONIC

C57BL/6NTac   These were originated in The Jackson Laboratory and then were transferred to NIH in 1974 and from there to Taconic in 1991.

C57BL/6JBomTac   These were originated in The Jackson Laboratory and then were transferred to Hannover in 1971 and from there to Taconic in 1988.

The JM8.N4 and JM8.F6 ES cells, used in the EUCOMM-KOMP projects, have been derived from C57BL/6N mice. Note added: According to a comment posted by Tom Fielder (please, read below), these ES cells are thought to be derived (and therefore, chimeras obtained must be bred to) from a C57BL/6N mouse, without any additional information from the actual provider used at the time. C57BL/6NTac mice are used for breeding chimeras. Same mouse strain, C57BL/6NTac, was used to derive the VGB6 ES cells, used by Regeneron and the KOMP projects too.

KNOWN GENETIC DIFFERENCES BETWEEN C57BL/6J and C57BL/6N mouse strains

Not all C57BL/6J mice available from different providers are absolutely genetically identical. Likewise, not all C57BL/6N mice available from different providers are genetically identical. But, what is more important is that C57BL/6J animals (the mouse strain used for the generation of many knock-out mouse models, reported and described and cryopreserved in repositoires world-wide) and C57BL/6N animals (the mouse strain choosen by the International knock-out projects) are DIFFERENT. This must be taken into account if you plan to breed new KO mice, generated from targeted ES cells provided by EUCOMM or KOMP projects, with former KO mice, most likely generated using c57BL/6J-derived ES cells.

GENE MUTATIONS

C57BL/6J mice carry a mutation in the nicotinamide nucleotide transhydrogenase (Nnt) gene, whereas C57BL/6N mice carry the wild-type allele for this locus. Exceptionally, the substrain C57BL/6JBomTac carry also the wild-type allele for the Nnt locus, suggesting that this mutation occurred in The Jackson Laboratory after 1971, when mice were sent to Hannover.

The C57BL/6JOlaHsd mice carry a mutation in the alpha-synuclein (Snca) gene, whereas, appearently, the rest of C57BL/6 mouse strains carry the wild-type allele for this locus.

As reported by Jennifer Moran, through the MGI-List, 19 SNPs were initially identified to distinguish the C57BL/6J and C57BL/6N mouse strains, with additional ~200 SNPs available to discriminate the various C57BL/6 mouse strains.

Eventually, we all hope these and other SNPs will become available through common mouse genetic databases to be used universally.

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3 Responses to “These black mice…”

  1. Tom says:

    I’d just like to add one comment regarding the JM8 ES cells from KOMP. These are listed on the KOMP website as being derived from C57BL/6N mice. When I inquired as to the exact substrain of C57BL/6N, I was told by Renee Araiza at UC-Davis that this information was not recorded at the time the cells were first derived, but it has been confirmed through subsequent SNP screening that the JM8 cells are “N.” They are using C57BL/6NTac mice to breed with JM8 chimeras.

    Also, Renee told me the VGB6 ES cells derived by Regeneron (also used by KOMP) are from C57BL/6NTac mice.

    regards,
    Tom Fielder

  2. Lluis says:

    Excellent addition Tom, I wasn’t 100% sure therefore I did not include it in the text, nor this information was posted in the EUCOMM or KOMP web sites. I will update the text with your comment and quote you.
    thanks, regards
    Lluis

  3. Lluis says:

    Thanks to a comment received from Kate Pritchett, from Charles River, it must be noted that, for UK-customers, there is currently a third additional C57BL/6 strain available from this animal provider, identified as “C57BL/6JCrl”, that will be eventually discontinued, due to the contract agreements in place between Charles River and The Jackson Laboratory.

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