Experiment
In the current study, subcongenic mapping was conducted to fine map the Tabw2 QTL on chromosome 6 previoulsy identified in B6.TH-Tabw2 congenic mice.
Four subcongenic lines were generated with smaller TH donor segments [Fig 1]:
B6.TH-(D6Mit273-D6Mit29), (Line A);
B6.TH-(D6Mit176-D6Mit291), (Line B);
B6.TH-(D6Mit29-D6Mit323), (Line C);
B6.TH-(D6MitMit301-D6Mit291), (Line D)
B6.TH-Tabw2 congenic mice showed a significantly larger fatpad weight than B6-homozygous control mice on both diets, therefore fat pad weight as the phenotypic trait used for fine mapping. For mapping, all the subcongenic mice, along with B6.TH-tabw2 congenic and B6-homozygous control mice were fed either chow or HFS diets, and their post-mortem fat pads were weighed.
Under chow feeding Line B had significantly greater fat pad weight than controls, comparable to that in B6.TH-Tabw2 congenic mice. The results suggest that the Tabw2 candidate region is most likely located within the unique segment retained in line B, extending distally from the marker D6Mit29.
Interestingly, lines C and D, two nested subcongenic lines of the line B, but not overlapping each other, exhibited fat pad weights numerically intermediate between B6-homozygous control and B6.TH-Tabw2 congenic mice (Table 1). This may suggest that the effect of Tabw2 on obesity could be attributed to at least two subloci, named Tabw2a (associated with line C) and Tabw2b (associated with line D).
Under HFS diet feeding all the subcongenic lines had significantly greater fat pad weight than B6-homozygous control mice, without genotype differences among the lines (Table 1). However, none of the subcongenic lines had fat pad weight that was as great as B6.TH-Tabw2 congenic mice.
Findings suggest that there are possibly at least two subloci, named Tabw2a and Tabw2b, responsible for the Tabw2-mediated obesity on chow. The maximal interval for tabw2a would be a 38.5-Mb region between D6Mit29 and D6Mit254.
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