Characterization of Mice Ubiquitously Overexpressing Human 15-Lipoxygenase-1: Effect of Diabetes on Peripheral Neuropathy and Treatment with Menhaden Oil

<div>Effects of nerve growth factor (NGF), docosahexaenoic acid (DHA), or <svg height="9.10327pt" id="M63" style="vertical-align:-0.3499298pt" version="1.1" viewbox="-0.0498162 -8.75334 67.4094 9.10327" width="67.4094pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><path d="M719 650H483V622C553 619 576 606 581 560C585 532 588 487 588 394V148H585L167 650H20V622C67 618 88 610 109 585C127 562 129 557 129 484V264C129 173 126 124 123 93C118 44 92 31 35 28V0H272V28C204 32 181 44 176 95C173 124 170 172 170 264V515H172L598 -9H629V394C629 487 631 532 635 563C639 606 663 619 719 622V650Z"></path></g><g transform="matrix(.013,0,0,-0.013,9.568,0)"><path d="M692 302H438V274C537 267 543 260 543 188V103C543 61 531 48 511 37C489 26 458 20 424 20C231 20 146 188 146 333C146 517 258 630 411 630C507 630 582 597 606 474L634 480C627 546 622 601 619 636C586 643 510 665 426 665C230 665 44 552 44 321C44 122 191 -15 411 -15C491 -15 573 7 635 21C629 49 628 81 628 116V202C628 261 632 266 692 274V302Z"></path></g><g transform="matrix(.013,0,0,-0.013,18.863,0)"><path d="M493 503C489 551 484 614 483 650H43V622C120 616 128 611 128 525V126C128 40 120 34 40 28V0H312V28C221 34 213 40 213 126V307H316C407 307 412 296 424 227H453V420H424C412 355 407 346 316 346H213V584C213 613 216 616 246 616H322C398 616 419 607 436 579C449 559 455 539 464 499L493 503Z"></path></g><g transform="matrix(.013,0,0,-0.013,28.742,0)"><path d="M535 230V280H323V490H265V280H52V230H265V-3H323V230H535Z"></path></g><g transform="matrix(.013,0,0,-0.013,39.278,0)"><path d="M43 650V622C120 616 128 612 128 526V124C128 39 120 33 34 27V0H270C392 0 492 25 567 83C643 141 690 230 690 350C690 444 655 517 605 565C543 625 450 650 323 650H43ZM213 547C213 587 217 598 226 604C236 612 262 617 304 617C371 617 429 604 474 576C554 529 592 439 592 336C592 176 505 36 319 36C246 36 213 55 213 131V547Z"></path></g><g transform="matrix(.013,0,0,-0.013,48.716,0)"><path d="M729 650H468V622C546 615 554 610 554 527V365H213V527C213 610 221 616 297 622V650H38V622C120 616 128 611 128 527V123C128 39 120 34 40 28V0H303V28C221 34 213 40 213 123V322H554V123C554 39 546 34 460 28V0H728V28C647 34 639 39 639 123V527C639 610 647 615 729 622V650Z"></path></g><g transform="matrix(.013,0,0,-0.013,58.191,0)"><path d="M673 0V28C608 34 594 43 563 129C499 303 432 494 370 665L339 656L132 132C98 43 84 37 20 28V0H238V28C162 35 154 45 175 108C188 150 203 192 219 237H432C454 176 474 122 487 83S491 36 428 28V0H673ZM418 280H234C265 362 296 450 328 535H330L418 280Z"></path></g></svg> on neurite growth by dorsal root ganglion neurons derived from wild-type and 15-LOX-1 transgenic mice. Dorsal root ganglion neurons were collected and cultured as described in Section <a href="https://static-preview.hindawi.com/articles/jdr/volume-2021/5564477/figures/#sec2">2</a>. Afterwards, the effects of nerve growth factor (10 ng/ml), docosahexaenoic acid (40 <i>μ</i>M), or the combination of <svg height="9.10327pt" id="M64" style="vertical-align:-0.3499298pt" version="1.1" viewbox="-0.0498162 -8.75334 67.4094 9.10327" width="67.4094pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><path d="M719 650H483V622C553 619 576 606 581 560C585 532 588 487 588 394V148H585L167 650H20V622C67 618 88 610 109 585C127 562 129 557 129 484V264C129 173 126 124 123 93C118 44 92 31 35 28V0H272V28C204 32 181 44 176 95C173 124 170 172 170 264V515H172L598 -9H629V394C629 487 631 532 635 563C639 606 663 619 719 622V650Z"></path></g><g transform="matrix(.013,0,0,-0.013,9.568,0)"><path d="M692 302H438V274C537 267 543 260 543 188V103C543 61 531 48 511 37C489 26 458 20 424 20C231 20 146 188 146 333C146 517 258 630 411 630C507 630 582 597 606 474L634 480C627 546 622 601 619 636C586 643 510 665 426 665C230 665 44 552 44 321C44 122 191 -15 411 -15C491 -15 573 7 635 21C629 49 628 81 628 116V202C628 261 632 266 692 274V302Z"></path></g><g transform="matrix(.013,0,0,-0.013,18.863,0)"><path d="M493 503C489 551 484 614 483 650H43V622C120 616 128 611 128 525V126C128 40 120 34 40 28V0H312V28C221 34 213 40 213 126V307H316C407 307 412 296 424 227H453V420H424C412 355 407 346 316 346H213V584C213 613 216 616 246 616H322C398 616 419 607 436 579C449 559 455 539 464 499L493 503Z"></path></g><g transform="matrix(.013,0,0,-0.013,28.742,0)"><path d="M535 230V280H323V490H265V280H52V230H265V-3H323V230H535Z"></path></g><g transform="matrix(.013,0,0,-0.013,39.278,0)"><path d="M43 650V622C120 616 128 612 128 526V124C128 39 120 33 34 27V0H270C392 0 492 25 567 83C643 141 690 230 690 350C690 444 655 517 605 565C543 625 450 650 323 650H43ZM213 547C213 587 217 598 226 604C236 612 262 617 304 617C371 617 429 604 474 576C554 529 592 439 592 336C592 176 505 36 319 36C246 36 213 55 213 131V547Z"></path></g><g transform="matrix(.013,0,0,-0.013,48.716,0)"><path d="M729 650H468V622C546 615 554 610 554 527V365H213V527C213 610 221 616 297 622V650H38V622C120 616 128 611 128 527V123C128 39 120 34 40 28V0H303V28C221 34 213 40 213 123V322H554V123C554 39 546 34 460 28V0H728V28C647 34 639 39 639 123V527C639 610 647 615 729 622V650Z"></path></g><g transform="matrix(.013,0,0,-0.013,58.191,0)"><path d="M673 0V28C608 34 594 43 563 129C499 303 432 494 370 665L339 656L132 132C98 43 84 37 20 28V0H238V28C162 35 154 45 175 108C188 150 203 192 219 237H432C454 176 474 122 487 83S491 36 428 28V0H673ZM418 280H234C265 362 296 450 328 535H330L418 280Z"></path></g></svg> on neurite outgrowth were determined. Data are presented as the <svg height="9.10327pt" id="M65" style="vertical-align:-0.3499298pt" version="1.1" viewbox="-0.0498162 -8.75334 67.6442 9.10327" width="67.6442pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><path d="M797 0V26C739 32 732 36 732 103V296C732 394 682 449 605 449C576 449 550 437 529 423C504 407 475 389 446 366C425 418 382 449 334 449C303 449 279 437 253 421C222 403 201 385 180 371V452C135 432 85 419 41 411V388C99 379 102 374 102 310V103C102 38 93 32 27 26V0H238V26C189 32 180 38 180 103V338C210 363 250 390 289 390C351 390 377 348 377 275V103C377 37 368 32 306 26V0H520V26C465 32 456 38 456 101V296C456 314 455 326 453 338C491 369 529 390 565 390C628 390 653 345 653 274V107C653 36 642 32 583 26V0H797Z"></path></g><g transform="matrix(.013,0,0,-0.013,10.595,0)"><path d="M380 106C343 72 306 56 265 56C195 56 116 112 115 248C235 252 361 262 377 265C396 269 400 277 400 297C400 374 333 449 250 449H249C198 449 144 421 103 376S37 269 37 201C37 88 109 -12 232 -12C263 -12 332 6 395 84L380 106ZM225 412C281 412 315 364 314 312C314 297 308 292 290 292C232 290 176 289 120 289C135 370 180 412 225 412Z"></path></g><g transform="matrix(.013,0,0,-0.013,16.198,0)"><path d="M433 39L423 65C413 59 399 54 387 54C370 54 352 69 352 114V299C352 352 342 392 307 422C285 440 255 449 225 449C168 437 102 399 75 379C56 365 44 353 44 339C44 315 69 296 87 296C101 296 111 303 116 319C124 349 133 371 145 385C156 397 171 404 190 404C241 404 275 364 275 291V274C253 256 180 229 120 209C65 190 39 159 39 110C39 47 88 -12 159 -12C189 -12 237 25 277 52C282 35 288 21 301 8C312 -3 333 -12 348 -12L433 39ZM275 84C256 65 221 48 195 48C164 48 124 73 124 124C124 161 146 180 185 198C206 208 254 229 275 240V84Z"></path></g><g transform="matrix(.013,0,0,-0.013,21.788,0)"><path d="M524 0V26C466 32 460 36 460 104V297C460 393 411 449 331 449C302 449 276 437 248 419C223 402 201 387 181 372V451C137 432 90 420 42 411V388C96 378 102 374 102 310V104C102 38 97 33 29 26V0H246V26C187 32 181 36 181 104V339C211 365 250 390 290 390C357 390 381 345 381 276V109C381 40 374 32 315 26V0H524Z"></path></g><g transform="matrix(.013,0,0,-0.013,31.913,0)"><path d="M535 290V340H323V533H265V340H52V290H265V84H323V290H535ZM535 -22V28H52V-22H535Z"></path></g><g transform="matrix(.013,0,0,-0.013,42.449,0)"><path d="M409 504C401 567 396 607 392 642C354 654 312 665 266 665C137 665 60 583 60 487C60 374 161 325 225 290C300 250 355 215 355 141C355 68 311 21 235 21C131 21 86 122 71 183L41 176C48 128 61 42 68 21C78 16 93 8 118 0C142 -7 175 -15 216 -15C349 -15 438 69 438 174C438 287 344 333 265 374C186 414 138 449 138 522C138 576 172 631 249 631C336 631 363 562 380 499L409 504Z"></path></g><g transform="matrix(.013,0,0,-0.013,48.455,0)"><path d="M517 162C503 123 484 88 467 68C445 42 417 34 341 34C291 34 256 34 237 47C219 59 213 81 213 128V317H308C395 317 402 311 415 240H444V431H415C403 364 398 356 307 356H213V584C213 613 215 616 246 616H322C394 616 421 609 435 587C448 566 458 544 467 502L496 506C493 557 488 625 488 650H42V622C120 616 128 612 128 523V125C128 43 120 35 29 28V0H511C520 31 540 125 546 158L517 162Z"></path></g><g transform="matrix(.013,0,0,-0.013,55.839,0)"><path d="M861 0V28C774 35 771 41 768 147L759 509C756 612 762 614 851 622V650H681L449 149L221 650H57V622C148 613 153 609 144 479L130 271C123 166 117 123 111 88C104 46 85 34 26 28V0H259V28C192 35 169 42 167 90C166 130 166 173 170 256L185 541H187L411 7H431L675 555H679L683 147C683 41 680 35 598 28V0H861Z"></path></g></svg> in <i>μ</i>m per neuron. The number of mice used per group was 9. <svg height="13.532pt" id="M66" style="vertical-align:-3.4295pt" version="1.1" viewbox="-0.0498162 -10.1025 50.6052 13.532" width="50.6052pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.0091,0,0,-0.0091,0,-5.741)"><path d="M486 158C486 177 478 202 466 220C413 228 386 236 336 262C386 288 413 297 466 304C478 323 486 347 485 366C470 376 444 381 422 380C389 338 368 319 321 288C323 345 329 372 349 422C339 442 322 461 305 470C289 461 271 442 262 422C281 372 287 345 290 288C243 319 222 338 189 380C167 381 142 376 125 366C125 347 133 322 145 304C198 296 225 288 275 262C225 236 198 227 145 220C133 201 125 177 126 158C141 148 167 143 189 144C222 186 243 205 290 236C288 179 282 152 262 102C272 82 289 63 306 54C322 63 340 82 350 102C330 152 324 179 321 236C368 205 390 186 422 144C444 143 470 148 486 158Z"></path></g><g transform="matrix(.013,0,0,-0.013,6.079,0)"><path d="M570 304C570 398 525 448 414 448C385 448 343 445 312 434L329 511L321 518C297 504 262 482 244 460L233 411C195 397 159 381 128 358L135 332C160 347 189 360 224 373L111 -147C97 -210 84 -218 17 -231L13 -257L254 -247L259 -218L233 -216C183 -212 177 -202 189 -142L218 -1C238 -10 266 -12 283 -12C351 3 429 48 483 105C543 168 570 242 570 304ZM482 289C482 161 380 33 304 33C278 33 248 51 233 69L303 396C326 400 352 403 369 403C428 403 482 380 482 289Z"></path></g><g transform="matrix(.013,0,0,-0.013,17.421,0)"><path d="M512 -3V55L134 254V256L512 456V514L75 281V230L512 -3Z"></path></g><g transform="matrix(.013,0,0,-0.013,28.684,0)"><path d="M241 635C89 635 35 457 35 312C35 153 89 -12 240 -12C390 -12 443 166 443 312C443 466 390 635 241 635ZM238 602C329 602 354 454 354 312C354 172 330 22 240 22C152 22 124 173 124 313S148 602 238 602Z"></path></g><g transform="matrix(.013,0,0,-0.013,34.924,0)"><path d="M113 -12C146 -12 170 11 170 46C170 78 146 103 114 103S58 78 58 46C58 11 82 -12 113 -12Z"></path></g><g transform="matrix(.013,0,0,-0.013,37.888,0)"><path d="M241 635C89 635 35 457 35 312C35 153 89 -12 240 -12C390 -12 443 166 443 312C443 466 390 635 241 635ZM238 602C329 602 354 454 354 312C354 172 330 22 240 22C152 22 124 173 124 313S148 602 238 602Z"></path></g><g transform="matrix(.013,0,0,-0.013,44.128,0)"><path d="M153 550H386L412 615L406 623H120L82 318C104 327 142 338 184 338C294 338 347 275 347 187C347 112 305 39 221 39C160 39 119 71 97 89C88 97 80 96 71 90C59 80 50 67 49 57C48 45 52 36 66 23C80 9 123 -12 169 -12C221 -11 288 15 342 59C403 109 431 165 431 225C431 308 366 395 238 395C212 395 165 379 127 364L153 550Z"></path></g></svg> compared to their respective basal; <svg height="14.2262pt" id="M67" style="vertical-align:-3.429501pt" version="1.1" viewbox="-0.0498162 -10.7967 50.6052 14.2262" width="50.6052pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.0091,0,0,-0.0091,0,-5.741)"><path d="M556 236V289H337V504H275V289H56V236H275V-4H337V236H556Z"></path></g><g transform="matrix(.013,0,0,-0.013,6.079,0)"><path d="M570 304C570 398 525 448 414 448C385 448 343 445 312 434L329 511L321 518C297 504 262 482 244 460L233 411C195 397 159 381 128 358L135 332C160 347 189 360 224 373L111 -147C97 -210 84 -218 17 -231L13 -257L254 -247L259 -218L233 -216C183 -212 177 -202 189 -142L218 -1C238 -10 266 -12 283 -12C351 3 429 48 483 105C543 168 570 242 570 304ZM482 289C482 161 380 33 304 33C278 33 248 51 233 69L303 396C326 400 352 403 369 403C428 403 482 380 482 289Z"></path></g><g transform="matrix(.013,0,0,-0.013,17.421,0)"><path d="M512 -3V55L134 254V256L512 456V514L75 281V230L512 -3Z"></path></g><g transform="matrix(.013,0,0,-0.013,28.684,0)"><path d="M241 635C89 635 35 457 35 312C35 153 89 -12 240 -12C390 -12 443 166 443 312C443 466 390 635 241 635ZM238 602C329 602 354 454 354 312C354 172 330 22 240 22C152 22 124 173 124 313S148 602 238 602Z"></path></g><g transform="matrix(.013,0,0,-0.013,34.924,0)"><path d="M113 -12C146 -12 170 11 170 46C170 78 146 103 114 103S58 78 58 46C58 11 82 -12 113 -12Z"></path></g><g transform="matrix(.013,0,0,-0.013,37.888,0)"><path d="M241 635C89 635 35 457 35 312C35 153 89 -12 240 -12C390 -12 443 166 443 312C443 466 390 635 241 635ZM238 602C329 602 354 454 354 312C354 172 330 22 240 22C152 22 124 173 124 313S148 602 238 602Z"></path></g><g transform="matrix(.013,0,0,-0.013,44.128,0)"><path d="M153 550H386L412 615L406 623H120L82 318C104 327 142 338 184 338C294 338 347 275 347 187C347 112 305 39 221 39C160 39 119 71 97 89C88 97 80 96 71 90C59 80 50 67 49 57C48 45 52 36 66 23C80 9 123 -12 169 -12C221 -11 288 15 342 59C403 109 431 165 431 225C431 308 366 395 238 395C212 395 165 379 127 364L153 550Z"></path></g></svg> compared to their respective NGF-treated neuron; <svg height="11.8239pt" id="M68" style="vertical-align:-0.04979992pt" version="1.1" viewbox="-0.0498162 -11.7741 5.21047 11.8239" width="5.21047pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.0091,0,0,-0.0091,0,-5.741)"><path d="M458 122C446 142 422 163 404 170C370 149 335 141 272 139V142C272 216 281 255 311 281C280 309 275 350 272 418C335 417 370 407 404 387C422 394 447 415 458 436C447 456 424 477 402 484C370 463 335 455 272 453C276 506 282 532 312 584C297 610 275 636 253 647C232 636 208 610 194 584C223 532 230 506 234 453C171 455 136 463 102 484C84 477 60 456 48 436C60 415 84 393 102 387C136 407 171 417 234 418C231 350 226 309 195 281C226 255 231 214 234 139C171 141 136 149 102 170C84 163 60 142 48 122C60 101 84 79 102 72C136 93 171 103 234 104C230 35 224 8 195 -42C208 -69 232 -94 254 -106C274 -94 298 -69 312 -42C282 8 276 35 272 104C335 103 370 93 404 72C422 79 446 101 458 122Z"></path></g></svg>compared to their respective DHA-treated neurons; <svg height="12.2304pt" id="M69" style="vertical-align:-0.04990005pt" version="1.1" viewbox="-0.0498162 -12.1805 4.98213 12.2304" width="4.98213pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.0091,0,0,-0.0091,0,-5.741)"><path d="M263 363V584C343 572 363 521 380 464L408 470C399 526 392 562 387 596C376 598 367 601 353 604C328 612 296 617 263 617V693H228V615C122 603 67 532 67 453C67 376 123 329 193 300L228 284V41C132 52 93 131 75 189L45 181C54 130 66 71 73 50C113 24 170 9 228 9V-76H263V11C370 24 434 90 434 185C434 275 367 325 292 352L263 363ZM228 376C171 398 136 431 136 484C136 530 164 578 228 584V376ZM263 272L275 267C345 236 359 196 359 150C359 96 325 50 263 42V272Z"></path></g></svg>compared to wild-type combined <span class="nowrap"><svg height="9.10327pt" id="M70" style="vertical-align:-0.3499298pt" version="1.1" viewbox="-0.0498162 -8.75334 67.4094 9.10327" width="67.4094pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><path d="M719 650H483V622C553 619 576 606 581 560C585 532 588 487 588 394V148H585L167 650H20V622C67 618 88 610 109 585C127 562 129 557 129 484V264C129 173 126 124 123 93C118 44 92 31 35 28V0H272V28C204 32 181 44 176 95C173 124 170 172 170 264V515H172L598 -9H629V394C629 487 631 532 635 563C639 606 663 619 719 622V650Z"></path></g><g transform="matrix(.013,0,0,-0.013,9.568,0)"><path d="M692 302H438V274C537 267 543 260 543 188V103C543 61 531 48 511 37C489 26 458 20 424 20C231 20 146 188 146 333C146 517 258 630 411 630C507 630 582 597 606 474L634 480C627 546 622 601 619 636C586 643 510 665 426 665C230 665 44 552 44 321C44 122 191 -15 411 -15C491 -15 573 7 635 21C629 49 628 81 628 116V202C628 261 632 266 692 274V302Z"></path></g><g transform="matrix(.013,0,0,-0.013,18.863,0)"><path d="M493 503C489 551 484 614 483 650H43V622C120 616 128 611 128 525V126C128 40 120 34 40 28V0H312V28C221 34 213 40 213 126V307H316C407 307 412 296 424 227H453V420H424C412 355 407 346 316 346H213V584C213 613 216 616 246 616H322C398 616 419 607 436 579C449 559 455 539 464 499L493 503Z"></path></g><g transform="matrix(.013,0,0,-0.013,28.742,0)"><path d="M535 230V280H323V490H265V280H52V230H265V-3H323V230H535Z"></path></g><g transform="matrix(.013,0,0,-0.013,39.278,0)"><path d="M43 650V622C120 616 128 612 128 526V124C128 39 120 33 34 27V0H270C392 0 492 25 567 83C643 141 690 230 690 350C690 444 655 517 605 565C543 625 450 650 323 650H43ZM213 547C213 587 217 598 226 604C236 612 262 617 304 617C371 617 429 604 474 576C554 529 592 439 592 336C592 176 505 36 319 36C246 36 213 55 213 131V547Z"></path></g><g transform="matrix(.013,0,0,-0.013,48.716,0)"><path d="M729 650H468V622C546 615 554 610 554 527V365H213V527C213 610 221 616 297 622V650H38V622C120 616 128 611 128 527V123C128 39 120 34 40 28V0H303V28C221 34 213 40 213 123V322H554V123C554 39 546 34 460 28V0H728V28C647 34 639 39 639 123V527C639 610 647 615 729 622V650Z"></path></g><g transform="matrix(.013,0,0,-0.013,58.191,0)"><path d="M673 0V28C608 34 594 43 563 129C499 303 432 494 370 665L339 656L132 132C98 43 84 37 20 28V0H238V28C162 35 154 45 175 108C188 150 203 192 219 237H432C454 176 474 122 487 83S491 36 428 28V0H673ZM418 280H234C265 362 296 450 328 535H330L418 280Z"></path></g></svg>-</span>treated neurons.</div>

Journal of Diabetes Research

fig7

Figure 7

Figure 7: Characterization of Mice Ubiquitously Overexpressing Human 15-Lipoxygenase-1: Effect of Diabetes on Peripheral Neuropathy and Treatment with Menhaden Oil 

Figure 7 | Characterization of Mice Ubiquitously Overexpressing Human 15-Lipoxygenase-1: Effect of Diabetes on Peripheral Neuropathy and Treatment with Menhaden Oil 