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The 2019 book tells the story of the unlikely friendship between the four main characters as they try to help the boy find his way home and its distinctive drawings and quotes have been much shared on social media since its publication.
Luther star Elba will play the fox, Hollander who featured in The Ipcress File, Baptiste and The Night Manager will play the mole, In Treatment's Gabriel Byrne is the horse, and newcomer Jude Coward Nicoll is the boy.
The cast will voice the characters in the animated adaptation which brings the book's well-loved pictures to life.
Mackesy said: “The journey of making the film of The Boy, the Mole, the Fox and the Horse with my ridiculously talented and kind animation team has been a magical one. It’s so great to think the story will be in the nation's homes this Christmas – and I really hope it helps bring comfort, love and laughter.”
The animation will feature in BBC One's Christmas 2022 schedules and is being produced by JJ Abrams as part of his Bad Robot production company.
It will also include a musical score from Isobel Waller-Bridge, sister of Fleabag creator Phoebe Waller-Bridge.
BBC chief content officer Charlotte Moore said: “Charlie Mackesy’s heart-warming and inspirational story brought to life through NoneMore Productions’ and Bad Robot Productions’ beautiful animation, is about the importance of love, kindness and friendship.
"It’s the perfect fit for Christmas on the BBC and a reminder to us all about what really matters in this world."
Children's Christmas highlights at the BBC have previously included a number of Julia Donaldson adaptations such as The Gruffalo, The Gruffalo's Child, Stick Man and The Snail and The Whale.
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