Ming, I'm preparing to order genetically engineered mice. For background strain selection, what's the difference between C57BL/6N and C57BL/6J?

Actually, B6N and B6J share 99% identical gene sequences, and they are interchangeable for most experiments, with only minor sequence differences. Let's explore this in detail.

 

C57BL/6N vs. C57BL/6J: How to Choose
 

Origin
 

1921: The history of C57BL/6 mice dates back to 1921 when C.C. Little developed the C57BL/6 strain through inbreeding.
 

1947: The Jackson Laboratory in the United States acquired C57BL/6 from Little and named it C57BL/6J (B6J).
 

1951: The National Institutes of Health (NIH) introduced the 32nd generation of C57BL/6J from Jackson Laboratory, forming the substrain C57BL/6N (B6N).
 

C57BL/6 mice were chosen as the background strain for the first gene knockout mouse established in the late 1980s, due to their high inbreeding status, good reproductive performance, and high in vitro fertilization rates.

C57BL/6 was also the first mouse strain to have its genome fully sequenced. The International Knockout Mouse Consortium (IKMC) selected C57BL/6N as the standard background strain, creating over 20,000 gene knockout mice, with their gene functions analyzed by the International Mouse Phenotyping Consortium (IMPC).

B6N and B6J share 99% identical gene sequences, making them interchangeable for most experiments. However, there are some sequence differences between them, including 34 coding SNPs (single nucleotide polymorphisms), 2 coding small indels (insertion or deletion mutations), 146 non-coding SNPs, and 54 non-coding small indels.
 

Metabolism-Related Research
 

B6J carries a mutation in the Nnt (nicotinamide nucleotide transhydrogenase) gene, leading to impaired insulin secretion and mitochondrial function. Consequently, B6J mice exhibit abnormal glucose tolerance and impaired insulin secretion.

In B6N mice, the Pmch gene has an isoleucine-to-threonine mutation. These mice show higher oxygen consumption and lower glucose tolerance, but their circulating glucose levels and normal glucose tolerance are both higher than those of B6J mice.

In diet-induced obesity studies, B6N mice gain more weight on high-fat diets compared to B6J mice. B6N mice are suitable for sensitivity studies on obesity, metabolic syndrome, and type 2 diabetes.

 

Immunology-Related Research
 

Nlrp12 is associated with human autoinflammation and regulates immune cell trafficking and cytokine production.

B6J mice have a mutation in the C-terminal leucine-rich repeat region of the Nlrp12 gene, where arginine is mutated to lysine. This results in impaired chemokine production, compromised immune cell infiltration, and impaired pathogen clearance. B6J mice may not be suitable for studying neutrophil responses to immune system pathogens or functions. For such research, B6N mice are recommended.
 

Ophthalmology-Related Research
 

B6N and B6J mice show significant differences in vision, primarily due to their genetic mutations. B6N mice carry the Crb1rd8 gene mutation, which causes vision impairment and visible white spots in the fundus. B6J mice lack this mutation and have relatively normal vision.

B6N mice have significantly fewer retinal arteriovenous crossings on average compared to B6J mice and show differences in responses to light-induced choroidal neovascularization. Additionally, B6N mice are more prone to age-related retinal degeneration and vision loss as they age.

 

 

Cardiology-Related Research
 

B6N mice carry a Mylk3 gene mutation that leads to loss of MYLK3 protein expression, making them ideal models for studying cardiomyopathy and other cardiovascular diseases.

B6N and B6J share 99% identical gene sequences and are interchangeable for most experiments. B6N is commonly used as the background strain for genetically engineered mice by IKMC, Taconic Biosciences, and Charles River. Except for highly specific research areas, there is no significant difference between the two as background strains for genetic engineering.

In conclusion, when choosing C57 mice for experiments, it's important to not only understand the characteristics of C57BL/6 but also the differences between substrains. Researchers should carefully review relevant literature based on their research direction and objectives to ultimately select the appropriate mouse strain.

 

References:

[1] Mekada K, Yoshiki A. Substrains matter in phenotyping of C57BL/6 mice. Exp Anim. 2021 May 13;70(2):145-160. doi: 10.1538/expanim.20-0158Epub 2021 Jan 14. PMID: 33441510; PMCID: PMC8150240.

[2] Simon MM, Greenaway S, White JK, Fuchs H, Gailus-Durner V, Wells S, Sorg T, Wong K, Bedu E, Cartwright EJ, Dacquin R, Djebali S, Estabel J, Graw J, Ingham NJ, Jackson IJ, Lengeling A, Mandillo S, Marvel J, Meziane H, Preitner F, Puk O, Roux M, Adams DJ, Atkins S, Ayadi A, Becker L, Blake A, Brooker D, Cater H, Champy MF, Combe R, Danecek P, di Fenza A, Gates H, Gerdin AK, Golini E, Hancock JM, Hans W, Hölter SM, Hough T, Jurdic P, Keane TM, Morgan H, Müller W, Neff F, Nicholson G, Pasche B, Roberson LA, Rozman J, Sanderson M, Santos L, Selloum M, Shannon C, Southwell A, Tocchini-Valentini GP, Vancollie VE, Westerberg H, Wurst W, Zi M, Yalcin B, Ramirez-Solis R, Steel KP, Mallon AM, de Angelis MH, Herault Y, Brown SD. A comparative phenotypic and genomic analysis of C57BL/6J and C57BL/6N mouse strains. Genome Biol. 2013 Jul 31;14(7):R82. doi: 10.1186/gb-2013-14-7-r82IF:10.1Q1 . PMID: 23902802; PMCID: PMC4053787.

[3] Williams JL, Paudyal A, Awad S, Nicholson J, Grzesik D, Botta J, Meimaridou E, Maharaj AV, Stewart M, Tinker A, Cox RD, Metherell LA. Mylk3 null C57BL/6N mice develop cardiomyopathy, whereas Nnt null C57BL/6J mice do not. Life Sci Alliance. 2020 Mar 25;3(4):e201900593. doi: 10.26508/lsa.201900593IF: 3.3 Q1 . PMID: 32213617; PMCID: PMC7103425.

[4]https://mp.weixin.qq.com/s/kGX4BJtvw5rXsVnEDvCs5g

[5]https://www.larc.tsinghua.edu.cn/post/448

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