Π₯Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΡΡΠΈΠΊΠ° ΡΡΠ°Π½ΡΠΊΡΠΈΠΏΡΠΈΠΎΠ½Π½ΠΎΠΉ ΠΈ Π±Π΅Π»ΠΎΠΊ-ΡΠ²ΡΠ·ΡΠ²Π°ΡΡΠ΅ΠΉ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ ΠΏΡΠΎΠΌΠΎΡΠΎΡΠ° ΡΠ΅ΡΡΠΎΡΡΠ°Π½ΡΠΏΠΎΠ·ΠΎΠ½Π° LINE1 ΠΊΡΡΡΡ
ΠΠ²ΡΠΎΡ ΠΏΡΠΈΠ·Π½Π°ΡΠ΅Π»Π΅Π½ ΠΠΈΠΌΠ΅ ΠΡΠΊΡΡΠ½ΠΎΠ²Ρ Π·Π° ΠΎΠ±ΡΡΠ΅Π½ΠΈΠ΅ ΠΎΡΠ½ΠΎΠ²Π½ΡΠΌ ΡΠΊΡΠΏΠ΅ΡΠΈΠΌΠ΅Π½ΡΠ°Π»ΡΠ½ΡΠΌ ΠΌΠ΅ΡΠΎΠ΄Π°ΠΌ Π½Π° Π½Π°ΡΠ°Π»ΡΠ½ΠΎΠΌ ΡΡΠ°ΠΏΠ΅ Π½Π°ΡΡΠΎΡΡΠ΅ΠΉ ΡΠ°Π±ΠΎΡΡ. Π₯ΠΎΡΠ΅Π»ΠΎΡΡ Π±Ρ ΠΏΠΎΠ±Π»Π°Π³ΠΎΠ΄Π°ΡΠΈΡΡ Π²ΡΠ΅Ρ ΡΠΎΡΡΡΠ΄Π½ΠΈΠΊΠΎΠ² ΠΡΡΠΏΠΏΡ Π½Π΅ΠΊΠΎΠ΄ΠΈΡΡΡΡΠ΅ΠΉ ΠΠΠ Π·Π° ΠΏΠ»ΠΎΠ΄ΠΎΡΠ²ΠΎΡΠ½ΠΎΠ΅ ΠΎΠ±ΡΡΠΆΠ΄Π΅Π½ΠΈΠ΅ ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΠΎΠ² ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ. ΠΡΠΎΠ±ΡΡ Π±Π»Π°Π³ΠΎΠ΄Π°ΡΠ½ΠΎΡΡΡ Π°Π²ΡΠΎΡ Π²ΡΡΠ°ΠΆΠ°Π΅Ρ Π½Π°ΡΡΠ½ΠΎΠΌΡ ΡΡΠΊΠΎΠ²ΠΎΠ΄ΠΈΡΠ΅Π»Ρ ΠΠ»ΡΠ³Π΅ ΠΠ³ΠΎΡΠ΅Π²Π½Π΅ ΠΠΎΠ΄Π³ΠΎΡΠ½ΠΎΠΉ Π·Π° ΠΏΡΠ΅Π΄ΠΎΡΡΠ°Π²Π»Π΅Π½Π½ΡΡ ΡΠ΅ΠΌΡ ΠΈ ΠΎΠ³ΡΠΎΠΌΠ½ΡΡ ΠΏΠΎΠ΄Π΄Π΅ΡΠΆΠΊΡ, ΠΎΠΊΠ°Π·ΡΠ²Π°Π΅ΠΌΡΡ Π½Π° ΠΏΡΠΎΡΡΠΆΠ΅Π½ΠΈΠΈ Π²ΡΠ΅ΠΉ… Π§ΠΈΡΠ°ΡΡ Π΅ΡΡ >
- Π‘ΠΎΠ΄Π΅ΡΠΆΠ°Π½ΠΈΠ΅
- ΠΡΠ΄Π΅ΡΠΆΠΊΠ°
- ΠΠΈΡΠ΅ΡΠ°ΡΡΡΠ°
- ΠΡΡΠ³ΠΈΠ΅ ΡΠ°Π±ΠΎΡΡ
- ΠΠΎΠΌΠΎΡΡ Π² Π½Π°ΠΏΠΈΡΠ°Π½ΠΈΠΈ
Π‘ΠΎΠ΄Π΅ΡΠΆΠ°Π½ΠΈΠ΅
- Π‘ΠΠΠ‘ΠΠ ΠΠ‘ΠΠΠΠ¬ΠΠ£ΠΠΠ«Π₯ Π‘ΠΠΠ ΠΠ©ΠΠΠΠ Π¦Π΅Π»ΠΈ ΠΈ Π·Π°Π΄Π°ΡΠΈ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ
- ΠΡΠ½ΠΎΠ²Π½ΡΠ΅ ΠΏΠΎΠ»ΠΎΠΆΠ΅Π½ΠΈΡ, Π²ΡΠ½ΠΎΡΠΈΠΌΡΠ΅ Π½Π° Π·Π°ΡΠΈΡΡ
- ΠΠΠΠΠ ΠΠΠ’ΠΠ ΠΠ’Π£Π Π«
- 1. ΠΡΡΠΎΡΠΈΡ ΠΎΡΠΊΡΡΡΠΈΡ ΡΠ΅ΠΌΠ΅ΠΉΡΡΠ²Π° ΠΏΠΎΠ²ΡΠΎΡΠΎΠ² LINE
- 2. Π‘ΡΡΡΠΊΡΡΡΠ° ΠΏΠΎΠ²ΡΠΎΡΠΎΠ² LINE
- 3. ΠΠΎΠ½ΡΠ΅Π½ΡΡΡΠ½ΡΠ΅ ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°ΡΠ΅Π»ΡΠ½ΠΎΡΡΠΈ ΡΠ»Π΅ΠΌΠ΅Π½ΡΠΎΠ² LINE1 ΡΠ°Π·Π½ΡΡ Π²ΠΈΠ΄ΠΎΠ²
- 4. ΠΠ°ΡΠ΅Π³ΠΈΡΡΡΠΈΡΠΎΠ²Π°Π½Π½ΡΠ΅ ΡΠ΅ΡΡΠΎΡΡΠ°Π½ΡΠΏΠΎΠ·ΠΈΡΠΈΠΈ LINE
- 5. ΠΡΠ΅Π΄ΠΏΠΎΠ»Π°Π³Π°Π΅ΠΌΡΠ΅ ΠΌΠ΅Ρ Π°Π½ΠΈΠ·ΠΌΡ ΡΠ΅ΡΡΠΎΡΡΠ°Π½ΡΠΏΠΎΠ·ΠΈΡΠΈΠΈ ΡΠ»Π΅ΠΌΠ΅Π½ΡΠΎΠ² LINE
- 6. ΠΠΎΠ·Π΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ ΡΠ»Π΅ΠΌΠ΅Π½ΡΠΎΠ² LENE1 Π½Π° Π³Π΅Π½ΠΎΠΌ ΠΌΠ»Π΅ΠΊΠΎΠΏΠΈΡΠ°ΡΡΠΈΡ
- 7. ΠΡΠΎΠΌΠΎΡΠΎΡΠ½ΡΠ΅ ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°ΡΠ΅Π»ΡΠ½ΠΎΡΡΠΈ LENE
- 8. Π’ΠΊΠ°Π½Π΅ΡΠΏΠ΅ΡΠΈΡΠΈΡΠ½ΠΎΡΡΡ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΠΈ LINE
- 9. ΠΠ΅Π»ΠΊΠΈ, ΡΠ²ΡΠ·ΡΠ²Π°ΡΡΠΈΠ΅ΡΡ Ρ Π²ΠΈΠ΄ΠΎΡΠΏΠ΅ΡΠΈΡΠΈΡΠ½ΡΠΌΠΈ ΠΏΡΠΎΠΌΠΎΡΠΎΡΠ°ΠΌΠΈ ΡΠ»Π΅ΠΌΠ΅Π½ΡΠΎΠ²
- ΠΠΠ’ΠΠ ΠΠΠΠ« Π ΠΠΠ’ΠΠΠ«
- 1. ΠΡΠ΄Π΅Π»Π΅Π½ΠΈΠ΅ ΡΠ΄Π΅Ρ ΠΈ ΠΏΠΎΠ»ΡΡΠ΅Π½ΠΈΠ΅ ΡΠ΄Π΅ΡΠ½ΠΎΠ³ΠΎ ΡΠΊΡΡΡΠ°ΠΊΡΠ°
- 2. ΠΠΠ, ΠΏΠ»Π°Π·ΠΌΠΈΠ΄Ρ ΠΈ ΠΎΠ»ΠΈΠ³ΠΎΠ½ΡΠΊΠ»Π΅ΠΎΡΠΈΠ΄Ρ
- 3. ΠΠ΅ΡΠΎΠ΄ ΡΠΎΡΠΌΠΎΠΆΠ΅Π½ΠΈΡ Π² Π³Π΅Π»Π΅ (ΡΠ΅ΡΠ°ΡΠ΄Π°ΡΠΈΡ)
- 4. ΠΠ»Π΅ΠΊΡΡΠΎΡΠΎΡΠ΅ΡΠΈΡΠ΅ΡΠΊΠΎΠ΅ ΡΠ°Π·Π΄Π΅Π»Π΅Π½ΠΈΠ΅ Π±Π΅Π»ΠΊΠΎΠ² ΠΈ ΠΈΡ ΠΎΠΊΡΠ°ΡΠΈΠ²Π°Π½ΠΈΠ΅ Π² Π³Π΅Π»Π΅
- 5. ΠΠ½ΠΊΡΠ±Π°ΡΠΈΡ Π±Π΅Π»ΠΊΠΎΠ², ΠΈΠΌΠΌΠΎΠ±ΠΈΠ»ΠΈΠ·ΠΎΠ²Π°Π½Π½ΡΡ Π½Π° ΠΌΠ΅ΠΌΠ±ΡΠ°Π½Π΅ Ρ ΠΌΠ΅ΡΠ΅Π½ΠΎΠΉ ΠΠΠ (Π‘Π°ΡΠ·Π²Π΅ΡΡΠ΅ΡΠ½-Π±Π»ΠΎΡΡΠΈΠ½Π³)
- 6. ΠΠΌΠΌΡΠ½ΠΎΠ±Π»ΠΎΡΡΠΈΠ½Π³
- 7. ΠΠΎΠ½ΠΎΠΎΠ±ΠΌΠ΅Π½Π½Π°Ρ Ρ ΡΠΎΠΌΠ°ΡΠΎΠ³ΡΠ°ΡΠΈΡ Π±Π΅Π»ΠΊΠΎΠ²
- 8. ΠΡΡΠΈΠ½Π½Π°Ρ ΠΎΡΠΈΡΡΠΊΠ° Π±Π΅Π»ΠΊΠΎΠ²
- 9. ΠΠ΅ΠΏΡΡΠΌΠΎΠ΅ ΠΈΠΌΠΌΡΠ½ΠΎΡΠ»ΡΠΎΡΠ΅ΡΡΠ΅Π½ΡΠ½ΠΎΠ΅ ΠΎΠΊΡΠ°ΡΠΈΠ²Π°Π½ΠΈΠ΅
- 10. Π€Π»ΡΠΎΡΠ΅ΡΡΠ΅Π½ΡΠ½Π°Ρ Π³ΠΈΠ±ΡΠΈΠ΄ΠΈΠ·Π°ΡΠΈΡ in situ (FISH)
- 11. ΠΡΠ΄Π΅Π»Π΅Π½ΠΈΠ΅ ΠΠΠ. ΠΠΈΠ±ΡΠΈΠ΄ΠΈΠ·Π°ΡΠΈΡ ΠΏΠΎ Π‘Π°ΡΠ·Π΅ΡΠ½Ρ ΠΈ Π΄ΠΎΡ-Π±Π»ΠΎΡ Π³ΠΈΠ±ΡΠΈΠ΄ΠΈΠ·Π°ΡΠΈΡ
- 12. ΠΡΠ΄Π΅Π»Π΅Π½ΠΈΠ΅ Π ΠΠ. ΠΠ»Π΅ΠΊΡΡΠΎΡΠΎΡΠ΅Π· Π ΠΠ Π² ΡΠΎΡΠΌΠ°Π»ΡΠ΄Π΅Π³ΠΈΠ΄Π½ΠΎΠΌ Π°Π³Π°ΡΠΎΠ·Π½ΠΎΠΌ Π³Π΅Π»Π΅. ΠΠΎΠ·Π΅ΡΠ½Π±Π»ΠΎΡΡΠΈΠ½Π³
- 13. ΠΠΌΠΌΡΠ½ΠΎΠΏΡΠ΅ΡΠΈΠΏΠΈΡΠ°ΡΠΈΡ
- 14. ΠΠΌΠΌΡΠ½ΠΎΠΏΡΠ΅ΡΠ΅ΠΏΠΈΡΠ°ΡΠΈΡ Ρ ΡΠΎΠΌΠ°ΡΠΈΠ½Π°
- 15. ΠΠΎΠΌΠΏΡΡΡΠ΅ΡΠ½ΡΠ΅ ΠΌΠ΅ΡΠΎΠ΄Ρ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ 53 Π ΠΠΠ£ΠΠ¬Π’ΠΠ’Π«
- 1. Π’ΠΊΠ°Π½Π΅ΡΠΏΠ΅ΡΠΈΡΠΈΡΠ½ΠΎΡΡΡ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΠΈ L1 ΠΊΡΡΡΡ
- 2. ΠΠ΅Π½ΠΎΠΌΠ½Π°Ρ ΠΎΡΠ³Π°Π½ΠΈΠ·Π°ΡΠΈΡ LIRn. ΠΠ½Π°Π»ΠΈΠ· ΠΏΡΠΎΠΌΠΎΡΠΎΡΠ½ΠΎΠΉ ΠΎΠ±Π»Π°ΡΡΠΈ LIRn
- 3. ΠΡΡΠ²Π»Π΅Π½ΠΈΠ΅ Π±Π΅Π»ΠΊΠΎΠ², ΡΠ²ΡΠ·ΡΠ²Π°ΡΡΠΈΡ ΠΏΡΠΎΠΌΠΎΡΠΎΡ ΡΠ»Π΅ΠΌΠ΅Π½ΡΠΎΠ² L1 ΠΊΡΡΡΡ in vitro
- 4. ΠΠΏΡΠ΅Π΄Π΅Π»Π΅Π½ΠΈΠ΅ ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΠΎΠΉ ΠΌΠ°ΡΡΡ PRLP- ΠΈ nodel-ΡΠ²ΡΠ·ΡΠ²Π°ΡΡΠΈΡ Π±Π΅Π»ΠΊΠΎΠ². ΠΡΡΠΈΠ½Π½Π°Ρ ΠΎΡΠΈΡΡΠΊΠ° ΡΡΠΈΡ Π±Π΅Π»ΠΊΠΎΠ²
- 5. ΠΠ΄Π΅Π½ΡΠΈΡΠΈΠΊΠ°ΡΠΈΡ PRLP- ΠΈ nodel-ΡΠ²ΡΠ·ΡΠ²Π°ΡΡΠΈΡ Π±Π΅Π»ΠΊΠΎΠ²
- 6. ΠΠΏΡΠ΅Π΄Π΅Π»Π΅Π½ΠΈΠ΅ ΠΏΡΠ΅Π΄ΠΏΠΎΠ»Π°Π³Π°Π΅ΠΌΡΡ ΡΠΎΡΠ΅ΠΊ ΠΈΠ½ΠΈΡΠΈΠ°ΡΠΈΠΈ ΡΡΠ°Π½ΡΠΊΡΠΈΠΏΡΠΈΠΈ LIRn
- 7. Π‘ΠΎΡΡΠΎΡΠ½ΠΈΠ΅ ΠΌΠ΅ΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΡ Π³Π΅Π½ΠΎΠΌΠ½ΡΡ ΠΏΡΠΎΠΌΠΎΡΠΎΡΠΎΠ² LIRn ΠΈ Π²Π»ΠΈΡΠ½ΠΈΠ΅ ΠΌΠ΅ΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΠΏΡΠΎΠΌΠΎΡΠΎΡΠ° LIRn Π½Π° ΡΠ²ΡΠ·ΡΠ²Π°Π½ΠΈΠ΅ Ρ Π±Π΅Π»ΠΊΠ°ΠΌΠΈ Spl, Sp3 ΠΈ
- ΠΠ΅Π‘Π
- 8. ΠΠ·ΡΡΠ΅Π½ΠΈΠ΅ ΡΠ²ΡΠ·ΡΠ²Π°Π½ΠΈΡ Π±Π΅Π»ΠΊΠΎΠ² Spl, Sp3, ΠΠ΅Π‘Π 2 Ρ ΠΏΡΠΎΠΌΠΎΡΠΎΡΠ°ΠΌΠΈ LIRn in vivo
- ΠΠΠ‘Π£ΠΠΠΠΠΠ Π ΠΠΠ£ΠΠ¬Π’ΠΠ’ΠΠ
- ΠΠ«ΠΠΠΠ«
Π₯Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΡΡΠΈΠΊΠ° ΡΡΠ°Π½ΡΠΊΡΠΈΠΏΡΠΈΠΎΠ½Π½ΠΎΠΉ ΠΈ Π±Π΅Π»ΠΎΠΊ-ΡΠ²ΡΠ·ΡΠ²Π°ΡΡΠ΅ΠΉ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ ΠΏΡΠΎΠΌΠΎΡΠΎΡΠ° ΡΠ΅ΡΡΠΎΡΡΠ°Π½ΡΠΏΠΎΠ·ΠΎΠ½Π° LINE1 ΠΊΡΡΡΡ (ΡΠ΅ΡΠ΅ΡΠ°Ρ, ΠΊΡΡΡΠΎΠ²Π°Ρ, Π΄ΠΈΠΏΠ»ΠΎΠΌ, ΠΊΠΎΠ½ΡΡΠΎΠ»ΡΠ½Π°Ρ)
ΠΠ·ΡΡΠ΅Π½ΠΈΠ΅ Π³Π΅Π½ΠΎΠΌΠΎΠ² Π²ΡΡΡΠΈΡ ΡΡΠΊΠ°ΡΠΈΠΎΡ ΠΏΠΎΠΊΠ°Π·Π°Π»ΠΎ, ΡΡΠΎ ΠΎΠ½ΠΈ ΡΠΎΠ΄Π΅ΡΠΆΠ°Ρ ΠΎΠ³ΡΠΎΠΌΠ½ΠΎΠ΅ ΠΊΠΎΠ»ΠΈΡΠ΅ΡΡΠ²ΠΎ ΠΏΠΎΠ²ΡΠΎΡΡΡΡΠΈΡ ΡΡ ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°ΡΠ΅Π»ΡΠ½ΠΎΡΡΠ΅ΠΉ ΠΠΠ, ΡΡΠ½ΠΊΡΠΈΠΈ ΠΊΠΎΡΠΎΡΡΡ Π² ΠΏΠΎΡΠ»Π΅Π΄Π½Π΅Π΅ Π²ΡΠ΅ΠΌΡ ΡΠΎΠ»ΡΠΊΠΎ Π½Π°ΡΠΈΠ½Π°ΡΡ ΡΠ°ΡΠΊΡΡΠ²Π°ΡΡΡΡ. Π Π³Π΅Π½ΠΎΠΌΠ°Ρ ΠΌΠ»Π΅ΠΊΠΎΠΏΠΈΡΠ°ΡΡΠΈΡ ΠΏΠΎΠ²ΡΠΎΡΡΡΡΠΈΠ΅ΡΡ ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°ΡΠ΅Π»ΡΠ½ΠΎΡΡΠΈ ΠΠΠ ΡΠΎΡΡΠ°Π²Π»ΡΡΡ ΠΎΠΊΠΎΠ»ΠΎ 50%, Π² ΡΠΎ Π²ΡΠ΅ΠΌΡ ΠΊΠ°ΠΊ Π³Π΅Π½Ρ — ΠΌΠ΅Π½Π΅Π΅ 5%. Π‘ΡΠ΅Π΄ΠΈ ΠΏΠΎΠ²ΡΠΎΡΡΡΡΠΈΡ ΡΡ ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°ΡΠ΅Π»ΡΠ½ΠΎΡΡΠ΅ΠΉ ΠΠΠ ΠΌΠΎΠΆΠ½ΠΎ Π²ΡΠ΄Π΅Π»ΠΈΡΡ ΠΏΡΡΡ ΠΊΠ»Π°ΡΡΠΎΠ²: ΠΏΡΠΎΡΡΡΠ΅ ΠΏΠΎΠ²ΡΠΎΡΡ, Π½Π°ΠΏΡΠΈΠΌΠ΅Ρ (A)n, (CGG)nΡΠ΅Π³ΠΌΠ΅Π½ΡΠ½ΡΠ΅ Π΄ΡΠΏΠ»ΠΈΠΊΠ°ΡΠΈΠΈ, ΡΠΎΡΡΠΎΡΡΠΈΠ΅ ΠΈΠ· Π±Π»ΠΎΠΊΠΎΠ² Π΄Π»ΠΈΠ½ΠΎΠΉ ΠΏΡΠΈΠΌΠ΅ΡΠ½ΠΎ 30−100 Ρ.ΠΏ.Π½.- ΡΠ°Π½Π΄Π΅ΠΌΠ½ΠΎ ΠΏΠΎΠ²ΡΠΎΡΠ΅Π½Π½ΡΠ΅ ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°ΡΠ΅Π»ΡΠ½ΠΎΡΡΠΈ, ΡΠ°ΠΊΠΈΠ΅ ΠΊΠ°ΠΊ ΡΠ΅Π½ΡΡΠΎΠΌΠ΅ΡΡ ΠΈ ΡΠ΅Π»ΠΎΠΌΠ΅ΡΡΡΠ΅ΡΡΠΎΠΏΠΎΠ·ΠΈΡΠΎΠ²Π°Π½Π½ΡΠ΅ ΠΊΠΎΠΏΠΈΠΈ ΠΊΠ»Π΅ΡΠΎΡΠ½ΡΡ Π³Π΅Π½ΠΎΠ² — ΠΏΡΠΎΡΠ΅ΡΡΠΈΡΠΎΠ²Π°Π½Π½ΡΠ΅ ΠΏΡΠ΅Π²Π΄ΠΎΠ³Π΅Π½ΡΠΈ ΠΌΠΎΠ±ΠΈΠ»ΡΠ½ΡΠ΅ ΡΠ»Π΅ΠΌΠ΅Π½ΡΡ, ΡΠ°ΡΡΠΎ ΠΎΡΠ½ΠΎΡΠΈΠΌΡΠ΅ ΠΊ Π΄ΠΈΡΠΏΠ΅ΡΠ³ΠΈΡΠΎΠ²Π°Π½Π½ΡΠΌ ΠΏΠΎΠ²ΡΠΎΡΠ°ΠΌ (Lander et al, 2001). ΠΡΠΈ ΡΡΠΎΠΌ, Π±ΠΎΠ»ΡΡΡΡ ΡΠ°ΡΡΡ ΠΏΠΎΠ²ΡΠΎΡΡΡΡΠΈΡ ΡΡ ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°ΡΠ΅Π»ΡΠ½ΠΎΡΡΠ΅ΠΉ ΠΠΠ ΠΌΠ»Π΅ΠΊΠΎΠΏΠΈΡΠ°ΡΡΠΈΡ (ΠΏΡΠΈΠΌΠ΅ΡΠ½ΠΎ 40−45% Π³Π΅Π½ΠΎΠΌΠ°) ΡΠΎΡΡΠ°Π²Π»ΡΡΡ ΠΌΠΎΠ±ΠΈΠ»ΡΠ½ΡΠ΅ ΡΠ»Π΅ΠΌΠ΅Π½ΡΡ — ΡΡΠ°ΠΈΡΠΏΠΎΠ·ΠΎΠ½Ρ ΠΈ ΡΠ΅ΡΡΠΎΡΡΠ°ΠΏΡΠΏΠΎΠ·ΠΎΠΏΡ (Lander et al, 2001).
Π¨ΠΈΡΠΎΠΊΠΎΠ΅ ΡΠ°ΡΠΏΡΠΎΡΡΡΠ°Π½Π΅Π½ΠΈΠ΅ ΠΌΠΎΠ±ΠΈΠ»ΡΠ½ΡΡ ΡΠ»Π΅ΠΌΠ΅Π½ΡΠΎΠ² Π² Π³Π΅Π½ΠΎΠΌΠ°Ρ ΠΎΠ±ΡΡΠ»ΠΎΠ²Π»Π΅Π½ΠΎ ΡΡΡΠ΅ΡΡΠ²ΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΠ³ΠΎ ΠΌΠ΅Ρ Π°Π½ΠΈΠ·ΠΌΠ° ΡΠ°Π·ΠΌΠ½ΠΎΠΆΠ΅Π½ΠΈΡ ΡΡΠΈΡ ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°ΡΠ΅Π»ΡΠ½ΠΎΡΡΠ΅ΠΉ. ΠΠ΅ΠΊΠΎΡΠΎΡΡΠ΅ ΡΠ΅ΠΌΠ΅ΠΉΡΡΠ²Π° ΠΌΠΎΠ±ΠΈΠ»ΡΠ½ΡΡ ΡΠ»Π΅ΠΌΠ΅Π½ΡΠΎΠ² ΠΊΠΎΠ΄ΠΈΡΡΡΡ Π±Π΅Π»ΠΊΠΈ, Π½Π΅ΠΎΠ±Ρ ΠΎΠ΄ΠΈΠΌΡΠ΅ Π΄Π»Ρ ΠΏΠ΅ΡΠ΅ΠΌΠ΅ΡΠ΅Π½ΠΈΡ ΠΈ Π²ΡΡΡΠ°ΠΈΠ²Π°Π½ΠΈΡ Π² Π³Π΅Π½ΠΎΠΌ ΠΈΡ ΠΊΠΎΠΏΠΈΠΉ. Π’Π°ΠΊΠΈΠ΅ ΠΌΠΎΠ±ΠΈΠ»ΡΠ½ΡΠ΅ ΡΠ»Π΅ΠΌΠ΅Π½ΡΡ ΡΠ²Π»ΡΡΡΡΡ Π°Π²ΡΠΎΠ½ΠΎΠΌΠ½ΡΠΌΠΈ.
Π£ ΠΌΠ»Π΅ΠΊΠΎΠΏΠΈΡΠ°ΡΡΠΈΡ Π½Π°ΠΈΠ±ΠΎΠ»Π΅Π΅ ΡΠ°ΡΠΏΡΠΎΡΡΡΠ°Π½Π΅Π½Π½ΡΠΌ ΡΠ΅ΠΌΠ΅ΠΉΡΡΠ²ΠΎΠΌ Π°Π²ΡΠΎΠ½ΠΎΠΌΠ½ΡΡ ΠΌΠΎΠ±ΠΈΠ»ΡΠ½ΡΡ ΡΠ»Π΅ΠΌΠ΅Π½ΡΠΎΠ², ΡΠΎΠ΄Π΅ΡΠΆΠ°ΡΠΈΠΌ ΡΠΏΠΎΡΠΎΠ±Π½ΡΠ΅ ΠΊ ΠΏΠ΅ΡΠ΅ΠΌΠ΅ΡΠ΅Π½ΠΈΡ ΠΊΠΎΠΏΠΈΠΈ, ΡΠ²Π»ΡΠ΅ΡΡΡ ΡΠ΅ΠΌΠ΅ΠΉΡΡΠ²ΠΎ LINE1 (long interspersed nucleotide element 1). ΠΠ»Π΅ΠΌΠ΅Π½ΡΡ LINE1 Π·Π°Π½ΠΈΠΌΠ°ΡΡ ΠΏΡΠΈΠΌΠ΅ΡΠ½ΠΎ 10−20% Π³Π΅Π½ΠΎΠΌΠ° ΠΌΠ»Π΅ΠΊΠΎΠΏΠΈΡΠ°ΡΡΠΈΡ , ΠΎΠ½ΠΈ ΡΠΏΠΎΡΠΎΠ±Π½Ρ ΡΠ°Π·ΠΌΠ½ΠΎΠΆΠ°ΡΡΡΡ Π² Π³Π΅Π½ΠΎΠΌΠ΅ Ρ ΠΏΠΎΠΌΠΎΡΡΡ ΠΌΠ΅Ρ Π°Π½ΠΈΠ·ΠΌΠ° ΠΎΠ±ΡΠ°ΡΠ½ΠΎΠΉ ΡΡΠ°Π½ΡΠΊΡΠΈΠΏΡΠΈΠΈ ΠΏΠΎΡΡΠ΅Π΄ΡΡΠ²ΠΎΠΌ Π ΠΠ ΠΈΠ½ΡΠ΅ΡΠΌΠ΅Π΄ΠΈΠ°ΡΠ° ΠΈ ΠΏΠΎΡΡΠΎΠΌΡ ΡΠ²Π»ΡΡΡΡΡ ΡΠ΅ΡΡΠΎΡΡΠ°Π½ΡΠΏΠΎΠ·ΠΎΠ½Π°ΠΌΠΈ (Ostertag, Kazazian, 2001). ΠΠ΅Π»ΠΊΠΈ, ΠΊΠΎΠ΄ΠΈΡΡΠ΅ΠΌΡΠ΅ LINE1, ΡΠΏΠΎΡΠΎΠ±ΡΡΠ²ΡΡΡ ΡΠ΅ΡΡΠΎΡΡΠ°Π½ΡΠΏΠΎΠ·ΠΈΡΠΈΠΈ Π½Π΅ ΡΠΎΠ»ΡΠΊΠΎ ΡΡΠΈΡ ΡΠ»Π΅ΠΌΠ΅Π½ΡΠΎΠ², Π½ΠΎ ΠΈ Π΄ΡΡΠ³ΠΎΠΉ ΠΊΠ»Π΅ΡΠΎΡΠ½ΠΎΠΉ ΠΠΠ, Π² ΡΠΎΠΌ ΡΠΈΡΠ»Π΅ ΠΠΠ Π½Π΅Π°Π²ΡΠΎΠ½ΠΎΠΌΠ½ΡΡ ΡΠ΅ΡΡΠΎΡΡΠ°Π½ΡΠΏΠΎΠ·ΠΎΠ½ΠΎΠ² (Wei et al, 2001; Dewannieux et al, 2003).
ΠΠ°Π½Π½ΡΠ΅ ΠΎ ΡΡΠ½ΠΊΡΠΈΠΎΠ½ΠΈΡΠΎΠ²Π°Π½ΠΈΠΈ ΡΠ»Π΅ΠΌΠ΅Π½ΡΠΎΠ² LINE I ΠΈ ΠΈΡ Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎΠΉ ΡΠΎΠ»ΠΈ Π² ΡΠ΅ΠΊΠΎΠΌΠ±ΠΈΠ½Π°ΡΠΈΠΈ, ΡΠ΅ΠΏΠ°ΡΠ°ΡΠΈΠΈ Π΄Π²ΡΠ½ΠΈΡΠ΅Π²ΡΡ ΡΠ°Π·ΡΡΠ²ΠΎΠ², ΡΠ΅ΡΡΠΎΡΡΠ°Π½ΡΠΏΠΎΠ·ΠΈΡΠΈΠΈ ΠΊΠ»Π΅ΡΠΎΡΠ½ΠΎΠΉ ΠΠΠ, ΠΎΡΠ³Π°Π½ΠΈΠ·Π°ΡΠΈΠΈ ΡΡΡΡΠΊΡΡΡΡ Ρ ΡΠΎΠΌΠ°ΡΠΈΠ½Π°, Π³Π΅Π½ΠΎΠΌΠ½ΡΡ ΠΏΠ΅ΡΠ΅ΡΡΡΠΎΠΉΠΊΠ°Ρ ΠΈ ΡΠ΅Π³ΡΠ»ΡΡΠΈΠΈ ΡΡΠ°Π½ΡΠΊΡΠΈΠΏΡΠΈΠΈ Π±Π»ΠΈΠ·Π»Π΅ΠΆΠ°ΡΠΈΡ Π³Π΅Π½ΠΎΠ² Π±ΠΎΠ»ΡΡΠ΅ Π½Π΅ ΠΏΠΎΠ·Π²ΠΎΠ»ΡΡΡ ΡΠ°ΡΡΠΌΠ°ΡΡΠΈΠ²Π°ΡΡ ΠΏΠΎΠ²ΡΠΎΡΡ LINE1 Π»ΠΈΡΡ ΠΊΠ°ΠΊ «ΠΏΠ°ΡΠ°Π·ΠΈΡΠΈΡΠ΅ΡΠΊΡΡ» ΠΠΠ Π² Π³Π΅Π½ΠΎΠΌΠ°Ρ (Furano, 2000; Ostertag, Kazazian, 2001). Π‘Π²ΠΎΠ΅ Π²Π»ΠΈΡΠ½ΠΈΠ΅ Π½Π° Π³Π΅Π½ΠΎΠΌ ΡΠ»Π΅ΠΌΠ΅Π½ΡΡ LINE1 ΠΎΠΊΠ°Π·ΡΠ²Π°ΡΡ Π³Π»Π°Π²Π½ΡΠΌ ΠΎΠ±ΡΠ°Π·ΠΎΠΌ ΠΏΠΎΡΡΠ΅Π΄ΡΡΠ²ΠΎΠΌ ΡΠ΅ΡΡΠΎΡΡΠ°Π½ΡΠΏΠΎΠ·ΠΈΡΠΈΠΈ, ΡΡΠ΅Π±ΡΡΡΠ΅ΠΉ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΠΈ Π ΠΠ LINE1 ΠΈ ΠΊΠΎΠ΄ΠΈΡΡΠ΅ΠΌΡΡ ΠΈΠΌΠΈ Π±Π΅Π»ΠΊΠΎΠ². ΠΠ΅ΠΊΠΎΠ½ΡΡΠΎΠ»ΠΈΡΡΠ΅ΠΌΠ°Ρ ΡΠ΅ΡΡΠΎΡΡΠ°Π½ΡΠΏΠΎΠ·ΠΈΡΠΈΡ ΡΠ»Π΅ΠΌΠ΅Π½ΡΠΎΠ² LINE1 ΠΌΠΎΠΆΠ΅Ρ ΠΏΡΠΈΠ²ΠΎΠ΄ΠΈΡΡ ΠΊ Π½Π΅Π³Π°ΡΠΈΠ²Π½ΡΠΌ ΠΏΠΎΡΠ»Π΅Π΄ΡΡΠ²ΠΈΡΠΌ Π΄Π΅ΡΡΠ°Π±ΠΈΠ»ΠΈΠ·Π°ΡΠΈΠΈ Π³Π΅Π½ΠΎΠΌΠ° ΠΊΠ»Π΅ΡΠΎΠΊ (Bourc'his, Bestor, 2004). ΠΠ΅ΡΠΌΠΎΡΡΡ Π½Π° ΡΡΠΎ, ΡΠ΅ΡΡΠΎΡΡΠ°Π½ΡΠΏΠΎΠ·ΠΈΡΠΈΡ ΡΠ»Π΅ΠΌΠ΅Π½ΡΠΎΠ² LINE1 Π½Π΅ ΡΠ²Π»ΡΠ΅ΡΡΡ Π°Π±ΡΠΎΠ»ΡΡΠ½ΠΎ Π·Π°ΠΏΡΠ΅ΡΠ΅Π½Π½ΠΎΠΉ Ρ ΠΌΠ»Π΅ΠΊΠΎΠΏΠΈΡΠ°ΡΡΠΈΡ ΠΈ ΠΏΡΠΎΠΈΡΡ ΠΎΠ΄ΠΈΡ Π² ΠΎΠΏΡΠ΅Π΄Π΅Π»Π΅Π½Π½ΡΡ ΡΠΈΠΏΠ°Ρ ΠΊΠ»Π΅ΡΠΎΠΊ (Brouha et al, 2002; Ostertag et al, 2002; Prak et al, 2003). Π‘Π»Π΅Π΄ΠΎΠ²Π°ΡΠ΅Π»ΡΠ½ΠΎ, ΡΡΡΠ΅ΡΡΠ²ΡΠ΅Ρ ΡΠ΅ΡΠΊΠΈΠΉ ΠΊΠΎΠ½ΡΡΠΎΠ»Ρ Π°ΠΊΡΠΈΠ²Π°ΡΠΈΠΈ ΠΈ ΡΠ΅ΠΏΡΠ΅ΡΡΠΈΠΈ ΡΡΠΈΡ ΠΏΠΎΠ²ΡΠΎΡΠΎΠ² in vivo. ΠΠ΄Π½ΠΈΠΌ ΠΈΠ· Π³Π»Π°Π²Π½ΡΡ ΡΠΏΠΎΡΠΎΠ±ΠΎΠ² ΠΊΠΎΠ½ΡΡΠΎΠ»Ρ ΡΠ΅ΡΡΠΎΡΡΠ°Π½ΡΠΏΠΎΠ·ΠΈΡΠΈΠΈ ΡΠ»Π΅ΠΌΠ΅Π½ΡΠΎΠ² LINE1 ΡΠ²Π»ΡΠ΅ΡΡΡ ΡΠ΅Π³ΡΠ»ΡΡΠΈΡ ΠΈΡ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΠΈ. ΠΠΊΡΠΏΡΠ΅ΡΡΠΈΡ ΡΠ»Π΅ΠΌΠ΅Π½ΡΠΎΠ² LINE1 ΡΠΊΠ°Π½Π΅ΡΠΏΠ΅ΡΠΈΡΠΈΡΠ½Π°, ΠΎΠ΄Π½Π°ΠΊΠΎ ΠΌΠ΅Ρ Π°Π½ΠΈΠ·ΠΌΡ Π΅Π΅ ΡΠ΅Π³ΡΠ»ΡΡΠΈΠΈ Π΄ΠΎ ΡΠΈΡ ΠΏΠΎΡ ΠΌΠ°Π»ΠΎ ΠΈΠ·ΡΡΠ΅Π½Ρ. ΠΠ΅Π»ΠΊΠΈ, ΡΠΏΠ΅ΡΠΈΡΠΈΡΠ΅ΡΠΊΠΈ ΡΠ²ΡΠ·ΡΠ²Π°ΡΡΠΈΠ΅ ΡΠ΅Π³ΡΠ»ΡΡΠΎΡΠ½ΡΠ΅ ΡΠ°ΠΉΠΎΠ½Ρ ΡΠ»Π΅ΠΌΠ΅Π½ΡΠΎΠ² LINE1, ΠΈΠ³ΡΠ°ΡΡ Π²Π°ΠΆΠ½ΡΡ ΡΠΎΠ»Ρ Π² ΠΊΠΎΠ½ΡΡΠΎΠ»Π΅ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΠΈ ΡΡΠΈΡ ΡΠ΅ΡΡΠΎΡΡΠ°Π½ΡΠΏΠΎΠ·ΠΎΠ½ΠΎΠ². ΠΠΎΡΡΠΎΠΌΡ ΠΌΠΎΠΆΠ½ΠΎ ΠΎΠΆΠΈΠ΄Π°ΡΡ, ΡΡΠΎ ΠΈΠ·ΡΡΠ΅Π½ΠΈΠ΅ Π±Π΅Π»ΠΊΠΎΠ², ΡΠΏΠ΅ΡΠΈΡΠΈΡΠ΅ΡΠΊΠΈ ΡΠ²ΡΠ·ΡΠ²Π°ΡΡΠΈΡ ΠΏΡΠΎΠΌΠΎΡΠΎΡΠ½ΡΠ΅ ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°ΡΠ΅Π»ΡΠ½ΠΎΡΡΠΈ ΡΠ΅ΡΡΠΎΡΡΠ°Π½ΡΠΏΠΎΠ·ΠΎΠ½ΠΎΠ² LINE1, ΠΏΠΎΠ·Π²ΠΎΠ»ΠΈΡ ΠΏΡΠΈΠ±Π»ΠΈΠ·ΠΈΡΡΡΡ ΠΊ ΠΏΠΎΠ½ΠΈΠΌΠ°Π½ΠΈΡ ΠΌΠ΅Ρ Π°Π½ΠΈΠ·ΠΌΠΎΠ² ΡΠΊΠ°Π½Π΅ΡΠΏΠ΅ΡΠΈΡΠΈΡΠ½ΠΎΠΉ ΡΠ΅Π³ΡΠ»ΡΡΠΈΠΈ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΠΈ ΠΏΠΎΠ²ΡΠΎΡΠΎΠ² LINE1 Π² ΠΊΠ»Π΅ΡΠΊΠ°Ρ ΠΌΠ»Π΅ΠΊΠΎΠΏΠΈΡΠ°ΡΡΠΈΡ .
ΠΡΡΠ²Π»Π΅Π½ΠΈΠ΅ ΠΈ ΠΈΠ΄Π΅Π½ΡΠΈΡΠΈΠΊΠ°ΡΠΈΡ Π±Π΅Π»ΠΊΠΎΠ², ΡΠΏΠ΅ΡΠΈΡΠΈΡΠ΅ΡΠΊΠΈ ΡΠ²ΡΠ·ΡΠ²Π°ΡΡΠΈΡ ΠΏΡΠΎΠΌΠΎΡΠΎΡ ΡΠ΅ΡΡΠΎΡΡΠ°Π½ΡΠΏΠΎΠ·ΠΎΠ½Π° LINE1 ΠΊΡΡΡΡ, ΡΠ²Π»ΡΠ»ΠΎΡΡ ΠΏΡΠ΅Π΄ΠΌΠ΅ΡΠΎΠΌ Π½Π°ΡΡΠΎΡΡΠ΅ΠΉ ΡΠ°Π±ΠΎΡΡ.
Π¦Π΅Π»ΠΈ ΠΈ Π·Π°Π΄Π°ΡΠΈ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ.
Π¦Π΅Π»Ρ Π΄Π°Π½Π½ΠΎΠ³ΠΎ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ — ΠΈΠ·ΡΡΠ΅Π½ΠΈΠ΅ ΡΠ΅Π³ΡΠ»ΡΡΠΈΠΈ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΠΈ LINE1 ΠΊΡΡΡΡ (LIRn) — Π°Π½Π°Π»ΠΈΠ· ΡΡΠ°Π½ΡΠΊΡΠΈΠΏΡΠΈΠΎΠ½Π½ΠΎΠΉ ΠΈ Π±Π΅Π»ΠΎΠΊ-ΡΠ²ΡΠ·ΡΠ²Π°ΡΡΠ΅ΠΉ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ ΠΏΡΠΎΠΌΠΎΡΠΎΡΠ° ΡΠ΅ΡΡΠΎΡΡΠ°Π½ΡΠΏΠΎΠ·ΠΎΠ½Π° LIRn.
ΠΠ»Ρ Π΄ΠΎΡΡΠΈΠΆΠ΅Π½ΠΈΡ ΡΡΠΎΠΉ ΡΠ΅Π»ΠΈ Π±ΡΠ»ΠΈ ΠΏΠΎΡΡΠ°Π²Π»Π΅Π½Ρ ΡΠ»Π΅Π΄ΡΡΡΠΈΠ΅ ΠΊΠΎΠ½ΠΊΡΠ΅ΡΠ½ΡΠ΅ Π·Π°Π΄Π°ΡΠΈ:
1. ΠΡΠΎΠ°Π½Π°Π»ΠΈΠ·ΠΈΡΠΎΠ²Π°ΡΡ Ρ Π°ΡΠ°ΠΊΡΠ΅Ρ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΠΈ LIRn Π² ΡΠ°Π·Π½ΡΡ ΡΠΊΠ°Π½ΡΡ Π²ΡΠ±ΡΠ°ΡΡ Π΄Π»Ρ Π΄Π°Π»ΡΠ½Π΅ΠΉΡΠ΅Π³ΠΎ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ ΡΠΊΠ°Π½ΠΈ Ρ ΡΠ°Π·Π½ΡΠΌ ΡΡΠΎΠ²Π½Π΅ΠΌ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΠΈ Π±Π΅Π»ΠΊΠ° pORFL.
2. ΠΡΠΎΠ²Π΅ΡΡΠΈ ΠΏΠΎΠΈΡΠΊ ΡΠ΅Π³ΡΠ»ΡΡΠΎΡΠ½ΡΡ ΡΠ»Π΅ΠΌΠ΅Π½ΡΠΎΠ², ΠΈΠ·Π²Π΅ΡΡΠ½ΡΡ Π΄Π»Ρ ΠΏΡΠΎΠΌΠΎΡΠΎΡΠΎΠ² L1 Π΄ΡΡΠ³ΠΈΡ Π²ΠΈΠ΄ΠΎΠ², Π² ΠΏΠ΅ΡΠ²ΠΈΡΠ½ΠΎΠΉ ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°ΡΠ΅Π»ΡΠ½ΠΎΡΡΠΈ ΠΏΡΠΎΠΌΠΎΡΠΎΡΠ° LIRn ΠΊΠΎΠΌΠΏΡΡΡΠ΅ΡΠ½ΡΠΌΠΈ ΠΌΠ΅ΡΠΎΠ΄Π°ΠΌΠΈ.
3. ΠΡΡΠ²ΠΈΡΡ ΡΠ΄Π΅ΡΠ½ΡΠ΅ Π±Π΅Π»ΠΊΠΈ, ΡΠΏΠ΅ΡΠΈΡΠΈΡΠ΅ΡΠΊΠΈ ΡΠ²ΡΠ·ΡΠ²Π°ΡΡΠΈΠ΅ ΠΏΡΠΎΠΌΠΎΡΠΎΡ LIRn in vitro, Π² ΠΈΡΡΠ»Π΅Π΄ΡΠ΅ΠΌΡΡ ΡΠΊΠ°Π½ΡΡ . ΠΠΎΠ΄ΠΎΠ±ΡΠ°ΡΡ ΡΡΠ»ΠΎΠ²ΠΈΡ ΠΎΡΠΈΡΡΠΊΠΈ Π²ΡΡΠ²Π»Π΅Π½Π½ΡΡ Π±Π΅Π»ΠΊΠΎΠ² Ρ ΠΏΠΎΠΌΠΎΡΡΡ ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°ΡΠ΅Π»ΡΠ½ΡΡ ΠΈΠΎΠ½ΠΎΠΎΠ±ΠΌΠ΅Π½Π½ΠΎΠΉ ΠΈ Π°ΡΡΠΈΠ½Π½ΠΎΠΉ Ρ ΡΠΎΠΌΠ°ΡΠΎΠ³ΡΠ°ΡΠΈΠΉ. ΠΠΏΡΠ΅Π΄Π΅Π»ΠΈΡΡ ΠΈΡ .
β’ ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΡΡ ΠΌΠ°ΡΡΡ ΠΈ ΡΠ°ΠΉΡΡ ΡΠ²ΡΠ·ΡΠ²Π°Π½ΠΈΡ. ΠΠ΄Π΅Π½ΡΠΈΡΠΈΡΠΈΡΠΎΠ²Π°ΡΡ Π±Π΅Π»ΠΊΠΈ, ΡΠΏΠ΅ΡΠΈΡΠΈΡΠ΅ΡΠΊΠΈ ΡΠ²ΡΠ·ΡΠ²Π°ΡΡΠΈΠ΅ ΠΏΡΠΎΠΌΠΎΡΠΎΡ ΡΠ΅ΡΡΠΎΡΡΠ°Π½ΡΠΏΠΎΠ·ΠΎΠ½Π° LIRn.
4. ΠΠΏΡΠ΅Π΄Π΅Π»ΠΈΡΡ ΡΡΠ°ΡΡΡ ΠΌΠ΅ΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΠΏΡΠΎΠΌΠΎΡΠΎΡΠ° LIRn Π² ΠΈΡΡΠ»Π΅Π΄ΡΠ΅ΠΌΡΡ ΡΠΊΠ°Π½ΡΡ , ΠΈΠ·ΡΡΠΈΡΡ Π²Π»ΠΈΡΠ½ΠΈΠ΅ ΠΌΠ΅ΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΠΏΡΠΎΠΌΠΎΡΠΎΡΠ° LIRn Π½Π° ΡΠ²ΡΠ·ΡΠ²Π°Π½ΠΈΠ΅ Ρ Π½ΠΈΠΌ ΡΠ΄Π΅ΡΠ½ΡΡ Π±Π΅Π»ΠΊΠΎΠ².
5. ΠΠ΅ΡΠΎΠ΄ΠΎΠΌ ΠΈΠΌΠΌΡΠ½ΠΎΠΏΡΠ΅ΡΠΈΠΏΠΈΡΠ°ΡΠΈΠΈ Ρ ΡΠΎΠΌΠ°ΡΠΈΠ½Π° ΠΏΡΠΎΠ²Π΅ΡΠΈΡΡ Π°ΡΡΠΎΡΠΈΠ°ΡΠΈΡ Π²ΡΡΠ²Π»Π΅Π½Π½ΡΡ Π±Π΅Π»ΠΊΠΎΠ² Ρ ΠΏΡΠΎΠΌΠΎΡΠΎΡΠΎΠΌ LIRn Π² ΠΈΡΡΠ»Π΅Π΄ΡΠ΅ΠΌΡΡ ΡΠΊΠ°Π½ΡΡ in vivo.
ΠΡΠ½ΠΎΠ²Π½ΡΠ΅ ΠΏΠΎΠ»ΠΎΠΆΠ΅Π½ΠΈΡ, Π²ΡΠ½ΠΎΡΠΈΠΌΡΠ΅ Π½Π° Π·Π°ΡΠΈΡΡ.
1. Π Π΅ΡΡΠΎΡΡΠ°Π½ΡΠΏΠΎΠ·ΠΎΠ½Ρ LIRn ΠΈΠΌΠ΅ΡΡ ΡΠ°Π·Π½ΡΠΉ ΡΡΠΎΠ²Π΅Π½Ρ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΠΈ Π² ΡΠΊΠ°Π½ΡΡ ΠΊΡΡΡΡ: Π΄ΠΈΡΠΊΡΠ΅ΡΠ½ΡΠ΅ ΡΠΌΡΡΠ»ΠΎΠ²ΡΠ΅ ΡΡΠ°Π½ΡΠΊΡΠΈΠΏΡΡ LIRn ΠΈ Π±Π΅Π»ΠΎΠΊ pORFT ΡΠΈΠ½ΡΠ΅Π·ΠΈΡΡΡΡΡΡ Π² ΠΊΠ»Π΅ΡΠΊΠ°Ρ ΡΠ΅ΠΌΠ΅Π½Π½ΠΈΠΊΠΎΠ², Π½ΠΎ Π½Π΅ Π² ΠΊΠ»Π΅ΡΠΊΠ°Ρ ΠΏΠ΅ΡΠ΅Π½ΠΈ.
2. ΠΡΠΎΠΌΠΎΡΠΎΡ LIRn ΡΠ°ΡΡΠΈΡΠ½ΠΎ Π΄Π΅ΠΌΠ΅ΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ Π² ΠΊΠ»Π΅ΡΠΊΠ°Ρ , ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΡΡΡΡΠΈΡ Π±Π΅Π»ΠΎΠΊ pORFT.
3. ΠΠ΅Π»ΠΊΠΈ Sp3 ΠΈ ΠΠ΅Π‘Π 2, Π½ΠΎ Π½Π΅ YY1, Π²Π·Π°ΠΈΠΌΠΎΠ΄Π΅ΠΉΡΡΠ²ΡΡΡ Ρ ΠΏΡΠΎΠΌΠΎΡΠΎΡΠΎΠΌ LIRn in vitro ΠΈ in vivo.
ΠΠΠΠΠ ΠΠΠ’ΠΠ ΠΠ’Π£Π Π«.
Π²ΡΠ²ΠΎΠ΄Ρ.
1. Π ΡΠ΅ΠΌΠ΅Π½Π½ΠΈΠΊΠ°Ρ ΠΊΡΡΡΡ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΡΡΡΡΡΡ Π΄ΠΈΡΠΊΡΠ΅ΡΠ½ΡΠ΅ ΡΠΌΡΡΠ»ΠΎΠ²ΡΠ΅ ΡΡΠ°Π½ΡΠΊΡΠΈΠΏΡΡ ΡΠ΅ΡΡΠΎΡΡΠ°Π½ΡΠΏΠΎΠ·ΠΎΠ½Π° LIRn ΠΈ ΠΊΠΎΠ΄ΠΈΡΡΠ΅ΠΌΡΠΉ LIRn Π±Π΅Π»ΠΎΠΊ pORFL Π ΠΊΠ»Π΅ΡΠΊΠ°Ρ ΠΏΠ΅ΡΠ΅Π½ΠΈ, Π³Π΄Π΅ Π½Π΅ ΠΎΠ±Π½Π°ΡΡΠΆΠΈΠ²Π°Π΅ΡΡΡ Π±Π΅Π»ΠΎΠΊ pORFI, ΡΡΠ°Π½ΡΠΊΡΠΈΠ±ΠΈΡΡΠ΅ΡΡΡ Π΄ΠΈΡΠΏΠ΅ΡΡΠ½ΡΠΉ Π½Π°Π±ΠΎΡ ΡΠΌΡΡΠ»ΠΎΠ²ΡΡ ΠΈ Π°Π½ΡΠΈΡΠΌΡΡΠ»ΠΎΠ²ΡΡ Π ΠΠ LIRn.
2. ΠΡΠΎΠΌΠΎΡΠΎΡ LIRn ΡΠΎΠ΄Π΅ΡΠΆΠΈΡ Π½Π΅ΡΠΊΠΎΠ»ΡΠΊΠΎ Π²Π΅ΡΠΎΡΡΠ½ΡΡ ΡΠ°ΠΉΡΠΎΠ² ΠΈΠ½ΠΈΡΠΈΠ°ΡΠΈΠΈ ΡΡΠ°Π½ΡΠΊΡΠΈΠΏΡΠΈΠΈ, Π³Π»Π°Π²Π½ΡΠΉ ΠΈΠ· ΠΊΠΎΡΠΎΡΡΡ ΡΠ°ΡΠΏΠΎΠ»Π°Π³Π°Π΅ΡΡΡ Π² ΠΏΠΎΠ»ΠΎΠΆΠ΅Π½ΠΈΠΈ 54 ΠΏ.Π½. ΠΏΡΠΎΠΌΠΎΡΠΎΡΠ½ΠΎΠ³ΠΎ ΠΌΠΎΠ½ΠΎΠΌΠ΅ΡΠ°. ΠΠΎΠ»Π΅Π΅ 80% Π³Π΅Π½ΠΎΠΌΠ½ΡΡ ΠΊΠΎΠΏΠΈΠΉ LIRn Π½Π΅ ΡΠΎΠ΄Π΅ΡΠΆΠ°Ρ ΠΏΡΠΎΠΌΠΎΡΠΎΡΠ½ΠΎΠΉ ΠΎΠ±Π»Π°ΡΡΠΈ.
3. ΠΠ΅Π»ΠΊΠΈ Spl/Sp3, Π½ΠΎ Π½Π΅ YY1, ΡΠΏΠ΅ΡΠΈΡΠΈΡΠ½ΠΎ ΡΠ²ΡΠ·ΡΠ²Π°ΡΡΡΡ Ρ ΠΏΡΠΎΠΌΠΎΡΠΎΡΠΎΠΌ LIRn in vitro. Π‘Π°ΠΉΡ ΡΠ²ΡΠ·ΡΠ²Π°Π½ΠΈΡ ΡΡΠ°Π½ΡΠΊΡΠΈΠΏΡΠΈΠΎΠ½Π½ΡΡ ΡΠ°ΠΊΡΠΎΡΠΎΠ² Spl/Sp3 ΠΈΠ΄Π΅Π½ΡΠΈΡΠ΅Π½ ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°ΡΠ΅Π»ΡΠ½ΠΎΡΡΠΈ, ΡΠ°ΡΠΏΠΎΠ»Π°Π³Π°ΡΡΠ΅ΠΉΡΡ Π² ΠΏΠΎΠ»ΠΎΠΆΠ΅Π½ΠΈΡΡ 125−133 ΠΏ.Π½. ΠΏΡΠΎΠΌΠΎΡΠΎΡΠ½ΠΎΠ³ΠΎ ΠΌΠΎΠ½ΠΎΠΌΠ΅ΡΠ° LIRn.
4. ΠΡΠΎΠΌΠΎΡΠΎΡ LIRn ΡΠ°ΡΡΠΈΡΠ½ΠΎ Π΄Π΅ΠΌΠ΅ΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ Π² ΠΊΠ»Π΅ΡΠΊΠ°Ρ ΡΠ΅ΠΌΠ΅Π½Π½ΠΈΠΊΠΎΠ² ΠΈ ΠΏΠΎΠ»Π½ΠΎΡΡΡΡ ΠΌΠ΅ΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ Π² ΠΊΠ»Π΅ΡΠΊΠ°Ρ ΠΏΠ΅ΡΠ΅Π½ΠΈ ΠΊΡΡΡΡ. ΠΠ΅ΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ ΠΏΡΠΎΠΌΠΎΡΠΎΡΠ° LIRn ΡΠΌΠ΅Π½ΡΡΠ°Π΅Ρ ΡΠ²ΡΠ·ΡΠ²Π°Π½ΠΈΠ΅ Ρ ΠΏΡΠΎΠΌΠΎΡΠΎΡΠΎΠΌ Π±Π΅Π»ΠΊΠΎΠ² Spl/Sp3 in vitro ΠΈ Π²ΡΠ·ΡΠ²Π°Π΅Ρ ΡΠ²ΡΠ·ΡΠ²Π°Π½ΠΈΠ΅ Π±Π΅Π»ΠΊΠ° ΠΠ΅Π‘Π 2.
5. In vivo, Π±Π΅Π»ΠΎΠΊ ΠΠ΅Π‘Π 2 Π²Π·Π°ΠΈΠΌΠΎΠ΄Π΅ΠΉΡΡΠ²ΡΠ΅Ρ Ρ ΠΏΡΠΎΠΌΠΎΡΠΎΡΠΎΠΌ LIRn Π² ΠΊΠ»Π΅ΡΠΊΠ°Ρ ΡΠ΅ΠΌΠ΅Π½Π½ΠΈΠΊΠΎΠ² ΠΈ Π² ΠΊΠ»Π΅ΡΠΊΠ°Ρ ΠΏΠ΅ΡΠ΅Π½ΠΈ, Π° Π±Π΅Π»ΠΎΠΊ Sp3 — Π»ΠΈΡΡ Π² ΠΊΠ»Π΅ΡΠΊΠ°Ρ ΡΠ΅ΠΌΠ΅Π½Π½ΠΈΠΊΠΎΠ² ΠΊΡΡΡ.
6. ΠΡΠ΅Π΄Π»ΠΎΠΆΠ΅Π½Π° ΡΡ Π΅ΠΌΠ° ΡΠ΅ΠΏΡΠ΅ΡΡΠΈΠΈ ΡΡΠ°Π½ΡΠΊΡΠΈΠΏΡΠΈΠΈ Ρ ΠΌΠ΅ΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½Π½ΡΡ ΠΏΡΠΎΠΌΠΎΡΠΎΡΠΎΠ² LIRn ΠΏΡΠΈ ΡΡΠ°ΡΡΠΈΠΈ Π±Π΅Π»ΠΊΠ° ΠΠ΅Π‘Π 2 ΠΈ Π°ΠΊΡΠΈΠ²Π°ΡΠΈΠΈ ΡΡΠ°Π½ΡΠΊΡΠΈΠΏΡΠΈΠΈ Ρ Π½Π΅ΠΌΠ΅ΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½Π½ΡΡ ΠΏΡΠΎΠΌΠΎΡΠΎΡΠΎΠ² LIRn ΠΏΡΠΈ ΡΡΠ°ΡΡΠΈΠΈ ΡΡΠ°Π½ΡΠΊΡΠΈΠΏΡΠΈΠΎΠ½Π½ΠΎΠ³ΠΎ ΡΠ°ΠΊΡΠΎΡΠ° Sp3.
ΠΠ²ΡΠΎΡ ΠΏΡΠΈΠ·Π½Π°ΡΠ΅Π»Π΅Π½ ΠΠΈΠΌΠ΅ ΠΡΠΊΡΡΠ½ΠΎΠ²Ρ Π·Π° ΠΎΠ±ΡΡΠ΅Π½ΠΈΠ΅ ΠΎΡΠ½ΠΎΠ²Π½ΡΠΌ ΡΠΊΡΠΏΠ΅ΡΠΈΠΌΠ΅Π½ΡΠ°Π»ΡΠ½ΡΠΌ ΠΌΠ΅ΡΠΎΠ΄Π°ΠΌ Π½Π° Π½Π°ΡΠ°Π»ΡΠ½ΠΎΠΌ ΡΡΠ°ΠΏΠ΅ Π½Π°ΡΡΠΎΡΡΠ΅ΠΉ ΡΠ°Π±ΠΎΡΡ. Π₯ΠΎΡΠ΅Π»ΠΎΡΡ Π±Ρ ΠΏΠΎΠ±Π»Π°Π³ΠΎΠ΄Π°ΡΠΈΡΡ Π²ΡΠ΅Ρ ΡΠΎΡΡΡΠ΄Π½ΠΈΠΊΠΎΠ² ΠΡΡΠΏΠΏΡ Π½Π΅ΠΊΠΎΠ΄ΠΈΡΡΡΡΠ΅ΠΉ ΠΠΠ Π·Π° ΠΏΠ»ΠΎΠ΄ΠΎΡΠ²ΠΎΡΠ½ΠΎΠ΅ ΠΎΠ±ΡΡΠΆΠ΄Π΅Π½ΠΈΠ΅ ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΠΎΠ² ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ. ΠΡΠΎΠ±ΡΡ Π±Π»Π°Π³ΠΎΠ΄Π°ΡΠ½ΠΎΡΡΡ Π°Π²ΡΠΎΡ Π²ΡΡΠ°ΠΆΠ°Π΅Ρ Π½Π°ΡΡΠ½ΠΎΠΌΡ ΡΡΠΊΠΎΠ²ΠΎΠ΄ΠΈΡΠ΅Π»Ρ ΠΠ»ΡΠ³Π΅ ΠΠ³ΠΎΡΠ΅Π²Π½Π΅ ΠΠΎΠ΄Π³ΠΎΡΠ½ΠΎΠΉ Π·Π° ΠΏΡΠ΅Π΄ΠΎΡΡΠ°Π²Π»Π΅Π½Π½ΡΡ ΡΠ΅ΠΌΡ ΠΈ ΠΎΠ³ΡΠΎΠΌΠ½ΡΡ ΠΏΠΎΠ΄Π΄Π΅ΡΠΆΠΊΡ, ΠΎΠΊΠ°Π·ΡΠ²Π°Π΅ΠΌΡΡ Π½Π° ΠΏΡΠΎΡΡΠΆΠ΅Π½ΠΈΠΈ Π²ΡΠ΅ΠΉ ΡΠ°Π±ΠΎΡΡ.
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