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Les modèles animaux :

4.2

4.2.1 Les chimpanzés et les macaques

&@"-.6=7J(@"97@A.AB&7A5&@&B57.65.66B79"96=(A&7A"=!5&%_)A?&.7+&"A( =?5&] 5&@A"=!5&%&%(F&59==&?%&@.7+&"A.97@.,B&@&A"-?97.>B&@F&"B7=?9+.5 .66B7.A.?&>B.&@A@.6.5.?&"&5B.9!@&?F("-&J%&@=A.&7A@.7+&"A(@=?5&jI7?% &A5]v~|w[.&57%wuvzk]&69%'5&(A(639?.A.?&6&7ABA.5.@(=9B?5&%(F&59==&6&7A %B F"".7 %B  &A =9B? %& =9A&7A.&5@ A?.A&6&7A@ "97A?& 5&@ .7+&"A.97@ "-?97.>B&@ j"B5.++&Z B?"&55Z &A &?.7 v~}uk] .&7 >B_.5 ?&=?(@&7A& 5& 69%'5& >B. 6.6& 5& 6.&BH 5_.7+&"A.97=?5&ZA-&A.975 7@A.ABA&9+&5A-5?,&6&7A?(%B.A@97BA.5.@A.97=9B? %&@?.@97@(A-.>B&@%&=B.@wuvx]

&@ 6">B&@ @97A >B7A  &BH 5&@ @&B5@ =&A.A@ =?.6A&@ 797f-B6.7@ "=!5&@ %& @B==9?A&? B7& ?(=5."A.97 %B  =?'@ B7& .79"B5A.97 .7A?-(=A.>B& %& "97@A?B"A.97 %_%Bj -&.A&A5]wuuwk]

4.2.2 Les modèles de souris :

4.2.2.1 Les souris transgéniques :

&@@9B?.@7&@97A=@=&?6.@@.F&@B]9B?=@@&?9BA?&"&A.7"97F(7.&7AZ5&@ @9B?.@97A(A(69%.+.(&@,(7(A.>B&6&7A=9B?=&?6&AA?&5_&H=?&@@.97%&@=?9A(.7&@F.?5&@Z &A 6)6& 5_.7A(,?5.A( %B ,(796& %B ] & @97A %&@ @9B?.@ .66B7959,.>B&@ A95(?7A&@Z "=!5&@%&=?9%B.?&%&@F.?.97@%B.7+&"A.&BH]55&@@97A@9BF&7ABA.5.@(&@=9B?A&@A&? 5&@.7-.!.A&B?@%&5=95I6(?@&A&5@>B&5_&7A("F.?9B556.FB%.7&j]&!&?&A5]wuuw[ B57%&? &A 5] wuuxk] &=&7%7AZ "& 69%'5& 7& =&?6&A =@ 5 +9?6A.97 5_""" %D  5_!@&7"& %B ?&"I"5,& %& "&A  &A  5_!@&7"& %& 79BF&55& .7+&"A.97] .7@.Z %_BA?&@ 69%'5&@6B?.7@97A(A(6.@&7=5"&=9B?=9BF9.?(AB%.&?5&@%.++(?&7A@6("7.@6&@%&5 =A-9,&7'@&%B&A5_(5.6.7A.97F.?5&]

4.2.2.2 Les souris AAV-HBV :

& @97A %&@ @9B?.@ .66B79"96=(A&7A&@ A?7@%B.A&@ F&" B7 F&"A&B? F.?5Z 5_%&79F.?B@Z >B. "97A.&7A 5& ,(796& %B ] =?'@ .73&"A.97 =? F9.& .7A?F&.7&B@& %B F&"A&B?Z5&@=?9A(.7&@%B@97A=?9%B.A&@@9B@5&"97A?:5&%_B7=?969A&B?&7%9,'7&

z|  !8.785" "..8.)5"!"6!)&&$5"076/1!#."6!P$78!"!8  /'" 8 /) 516 13" $." 7510)48" !"6 !)&&$5"076 /1!#."6 "..8.)5"6 87).)6$6 3185 ."6 )0&" 7)106 !8  F "6 )/'"6!"6 C "3UL"7 "3V[6107!"63(171'53()"6&)7"6!06.".1571)5"F "6)/'"6!"6 "3UFUFTX"7 "36107!37$"65"63" 7)9"/"07!"NF0'"7.FUSTTD().)33"5)310"7.FUSSUOF    "5 7$5)67)48"6!"6/1!#."6 "..8.)5"6(8/)0687).)6$63185.G)0&" 7)1035."  (48" /1!#." "67 35$6"07$ 9"  6"6 907'"6 "7 6"6 )0 109$0)"076 N)'85" !37$" !" ..:")66 "7 0!5) USTYOF

z} %Bj.7,9JJ.&A5]wuuxk]&69%'5&=&?6.@5_(AB%&%&5_(5.6.7A.97F.?5&69%B5(& =?5&@I@A'6&.66B7.A.?&&A79A66&7A5&?:5&%&@AB?5 .55&?.7@.>B&5=&?@.@A7"& %&5_.7+&"A.97j7,&A5]wuvyk] &69%'5&=?(@&7A&>B&5>B&@.7"97F(7.&7A@] 57&@_,.A=@%_B7&.7+&"A.977AB?&55& &A"&?A.7@=?6'A?&@7&=&BF&7A%97"=@)A?&(AB%.(@]&=5B@Z5=?(@&7"&%BF&"A&B? F.?5 =&BA .7%B.?& %&@ .7A&?+(?&7"&@ B 7.F&B %B @I@A'6& .66B7.A.?& &A 5 +9?6A.97 %& 5_"""%B&@A@9BF&7A?&@A?&.7A&]&=&7%7AZ%7@5&5!9?A9.?&Z79B@F97@?(B@@. %(697A?&? 5_(A!5.@@&6&7A %_B7 =995 %_""" =? 9BA-&?7 59AZ %7@ %&@ @9B?.@ z|{ A?7@%B.A&@F&"5&F&"A&B?}fj B5.&B".+9?&A5]wuv|k

4.2.2.3 Injection hydrodynamique dans les souris :

5 @_,.A %_B7& 6(A-9%& =&?6&AA7A %_.73&"A&? 5&  %7@ 5 @9B?.@] _&@A B7& A&"-7.>B&&++.""&=&?6&AA7A%&A?7@+(?&?5&6A(?.&5,(7(A.>B&%7@5&+9.&%&5@9B?.@] &5"97@.@A&&7B7&?=.%&.73&"A.97%_B7&,?7%&>B7A.A(%&5.>B.%&"97A&77A5_%7@ 5F&.7&%&5>B&B&%&5@9B?.@=&?6&AA7AB7&!@9?=A.97%&5_%7@5&@-(=A9"IA&@ &A5_&H=?&@@.97A?7@.A9.?&%&5_%Bj].BZ97,Z&A.Bv~~~k]

& 69%'5&  =&?6.@ %& %(5.F?&? 5& ,(796& %B  %7@ B7& @9B?.@ .66B79"96=(A&7A& &A .7@. %_(AB%.&? 5_(F5BA.97 %& "96=9@(@ 7A.F.?BHZ 5_&++&A 7A.F.?5 %&@.7A&?+(?&7A@.7@.>B&"&5B.%B@I@A'6& d@~j]f].7&A5]wuvyk]

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4.2.2.4 Les souris humanisées :

5 @_,.A %_B7 69%'5& 9C 5& +9.& 6B?.7 &@A ?&6=5"( =? %&@ "&55B5&@ -(=A.>B&@ -B6.7&@ &7A?.77A 5 =&?6.@@.F.A( %&@ @9B?.@ B ] 9B? "&5Z .5 &@A 7("&@@.?& >B& 5 ?(=97@& .66B7.A.?& %=AA.F& %& 5 @9B?.@ @9.A !95.& =9B? =&?6&AA?& 5 @B?F.& %&@ -(=A9"IA&@-B6.7@A?7@=57A(@]?(,(7(?A.97%B+9.&=&BA=?&7%?&>B&5>B&A&6=@&A =&BA)A?&"97A?:5(&&76&@B?7A5"97"&7A?A.97%7@5&@(?B6%&5_5!B6.7&-B6.7&]

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F.?5

1 Biologie de l’ADNccc

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 7& "96=9?A& =@ %_9?.,.7& %& ?(=5."A.97 j kZ .5 7_&@A %97" =@ ?(=5.>B( =? 5&@ =95I6(?@&@ "&55B5.?&@ 59?@ %& 5 6.A9@&] 9?@ %& 5 %.F.@.97 "&55B5.?&Z .5 &@A A?7@6.@ BH "&55B5&@+.55&@=?%.++B@.97=@@.F&]

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Structure du minichromosome

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