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Aviva Premiership rivals Northampton and Harlequins will both give youth a chance in their opening match in this season's LV= Cup.
With international commitments taking their toll, Saints head coach Jim Mallinder has handed a debut to Tom Stephenson in the centres.
There are a further five players who could make their first appearances off the bench; props Ethan Waller and Danny Herriott, scrum-half Alex Day and backs Anders Mogensen and Tom Collins are all amongst the replacements.
Ryan Lamb starts at fly-half and Luther Burrell returns to partner Stephenson in the centres in a team that is captained by flanker Calum Clark.
Quins are without several regulars themselves, with five of their players picked in the England squad to face Fiji at Twickenham this weekend.
Rory Clegg and Charlie Walker have also been ruled out through injury this week, joining Will Skinner, George Merrick and Ross Chisholm on the sidelines.
Ben Botica starts at fly-half, alongside Karl Dickson, for the tough trip to Franklin's Gardens.
Pete Browne and Joe Trayfoot make their first start of the season, while open side flanker Luke Wallace captains the side for the first time.
Jack Clifford, Jordan Burns, Louis Grimoldby and Miles Mantella will make their first senior appearances for the club if they are used from the bench.
Northampton: 15 Tom May, 14 Scott Armstrong, 13 Tom Stephenson, 12 Luther Burrell, 11 Jamie Elliott, 10 Ryan Lamb, 9 Martin Roberts, 8 GJ Van Velze, 7 Ben Nutley, 6 Calum Clarke (c), 5 Rhys Oakley, 4 Mark Sorenson, 3 Paul Doran Jones, 2 Mike Haywood, 1 Alex Waller.
Replacements: 16 Ross McMillan, 17 Ethan Waller, 18 Danny Herriott, 19 Christian Day, 20 Teimana Harrison, 21 Alex Day, 22 Anders Mogenson, 23 Tom Collins.
Harlequins: 15 Ollie Lindsay-Hague, 14 Seb Stegmann, 13 Matt Hopper, 12 Harry Sloan, 11 Sam Smith, 10 Ben Botica, 9 Karl Dickson, 8 Tom Guest, 7 Luke Wallace (c), 6 Joe Trayfoot, 5 Charlie Matthews, 4 Pete Browne, 3 Will Collier, 2 Dave Ward, 1 Mark Lambert.
Replacements: 16 Rob Buchanan, 17 Darryl Marfo, 18 Kyle Sinckler, 19 Sam Twomey, 20 Jack Clifford, 21 Jordan Burns, 22 Louis Grimoldby, 23 Miles Mantella.
"We have been impressed by the Senior Academy youngsters in training and in the Aviva 'A' League.
"The LV= Cup gives us a perfect opportunity to see if they can take a step up in intensity and competitiveness, as well as giving much needed game time for first team squad members.
"We believe that the team which has been named has the ability to get a good result against Harlequins tomorrow."
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|Saturday 25th January|
|15:00||Scarlets vs Gloucester|
|15:00||Harlequins vs Leicester|
|15:00||Bath vs Cardiff Blues|
|15:00||Exeter vs Ospreys|
|15:00||Newport Gwent D'gons vs Northampton|
|15:00||Wasps vs London Irish|
|15:00||Sale Sharks vs Worcester|
|15:00||Saracens vs Newcastle|
|Saturday 1st February|
|15:00||Newcastle vs Newport Gwent D'gons|
|15:00||Gloucester vs Wasps|
|15:00||Ospreys vs Sale Sharks|
|15:00||Cardiff Blues vs Harlequins|
|15:00||Worcester vs Exeter|
|15:00||Leicester vs Bath|
|15:00||Northampton vs Saracens|
|15:00||London Irish vs Scarlets|
|Sunday 17th November|
|London Irish 18 - 39 Northampton|
|Saracens 51 - 10 Scarlets|
|Bath 37 - 15 Exeter|
|Saturday 16th November|
|Gloucester 20 - 3 Newcastle|
|Newport Gwent D'gons 20 - 8 Wasps|
|Friday 15th November|
|Harlequins 26 - 31 Sale Sharks|
|Worcester 18 - 21 Leicester|
|Ospreys 13 - 21 Cardiff Blues|
|Sunday 10th November|
|Newcastle 29 - 21 London Irish|
|Saturday 9th November|
|Northampton 33 - 6 Gloucester|
|Exeter 19 - 5 Harlequins|
|Friday 8th November|
|Sale Sharks 20 - 27 Bath|
|Leicester 39 - 16 Ospreys|
|Scarlets 21 - 13 Newport Gwent D'gons|
|Wasps 21 - 24 Saracens|
|Cardiff Blues 16 - 21 Worcester|
Read the thoughts and opinions of Stuart Barnes with skysports.com