Frequently Asked Questions: The Nnt Mutation in C57BL/6J
The identification of the nicotinamide nucleotide transhydrogenase (Nnt) deletion in C57BL/6J (B6/J) has led many investigators to inquire about how this mutation may affect the phenotype of their mutant mice.
What is the Nnt mutation in the B6/J?
A spontaneous deletion eliminating exons 7-14 in the Nnt gene arose in B6/J sometime between 1976 and 1984.
What is the function of the Nnt gene?
The Nnt gene encodes a mitochondrial protein that catalyzes production of NADPH which participates in ATP synthesis.
What effect does the Nnt mutation have in mice?
B6/J mice have a normal life span, and manifest no overt abnormalities indicating that Nnt is not critical for normal physiological function. The mutation has been linked to more robust weight gain on a high fat diet.
Are B6/J mice diabetic as a consequence of the Nnt deletion?
No. B6/J mice show moderately impaired glucose clearance and resting glucose levels slightly higher then wildtype Nnt mice; however, glucose levels are below the diabetic threshold.
Does Nnt affect B6/J response to diet-induced obesity (DIO)?
B6/J males on a 60kcal % fat diet for 14 weeks, weighed more, had higher non-fasting plasma glucose levels, and were more severely glucose intolerant than C57BL/6NJ (B6/NJ) males, which are wild-type for the Nnt allele. For additional information view JAX® NOTES issue 551 article.
Is the Nnt deletion required for a robust DIO response?
No. B6/J males do respond more robustly to DIO; however, B6/NJ mice develop DIO, and NON/ShiLtJ (also with a wild-type Nnt) males are even more DIO-responsive. View a DIO strain comparison article.
Which B6 strain is best for my studies, the B6/J strain or its substrain the B6/NJ?
Using a consistent strain background will promote generation of more consistent data. The B6/J is the most published, best characterized mouse model available and has been the background of choice for thousands of genetically engineered mice. Also consider that the genotypic and phenotypic profiles of the B6/J and B6/NJ are different and one may be advantageous over the other for some studies. The B6/J, for example, gains weight faster on a high fat diet and is considered a desirable trait for many metabolic studies. Review the literature and consider what backgrounds have been used in your area of research or consider trying both strains if you are doing a pilot study. Both the B6/J and the B6/NJ are available from the Jackson Laboratory and are part of our unique Genetic Stability Program to drastically reduce genetic drift.
Do researchers need to test for the Nnt mutation in their mouse models?
Not unless you have specific scientific-based reasons for ensuring you have a functional Nnt gene. The Nnt mutation does not have adverse effects on the lifespan or integrity of the B6/J mouse. In fact, the B6/J is known for its longevity compared to other inbred strains. Every mouse model, including the B6/J and B6/NJ, is genetically distinct with known phenotypic characteristics that make it useful in a wide variety of research areas.
How does The Jackson Laboratory limit genetic drift in their most popular strains?
Our Genetic Stability Program (GSP) ensures genetic integrity and limits genetic drift of JAX® Mice. For details, see our Genetic Stability Program website.
