An HLA-Transgenic Mouse Model of Type 1 Diabetes That Incorporates the Reduced but Not Abolished Thymic Insulin Expression Seen in Patients

<div>Diabetes development in NOD and NOD.Ins<svg height="12.338pt" id="M66" style="vertical-align:-0.04979992pt" version="1.1" viewbox="-0.0498162 -12.2882 18.7081 12.338" width="18.7081pt" 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="M414 144C384 79 371 75 317 75H135L276 221C367 316 408 376 408 465C408 570 327 635 237 635C179 635 131 609 100 575L42 494L67 471C94 510 138 565 205 565C277 565 321 517 321 435C321 348 258 270 195 195C146 137 88 81 33 26V0H411C423 44 433 88 446 135L414 144Z" id="g50-51"></path><glyph.data ascent="3443" descent="-2856" horiz-adv-x="487" vert-adv-y="487"></glyph.data></g><g transform="matrix(.0091,0,0,-0.0091,6.331,-5.872)"><path d="M522 0V30C462 35 455 41 455 106V280C455 397 397 451 314 451C262 451 206 414 171 379V710C131 698 69 682 20 675V647C87 642 90 637 90 574V106C90 41 80 35 20 30V0H236V30C176 35 171 43 171 106V339C198 371 237 391 276 391C341 391 374 350 374 269V106C374 43 367 35 308 30V0H522Z" id="g58-102"></path><glyph.data ascent="1007" descent="-369" horiz-adv-x="544" vert-adv-y="544"></glyph.data></g><g transform="matrix(.0091,0,0,-0.0091,11.254,-5.872)"><path d="M384 109C349 76 310 59 268 59C197 59 123 113 120 245C240 248 367 259 384 262C403 266 407 275 407 296C407 376 338 451 254 451H253C201 451 148 425 105 378C65 334 39 272 39 203C39 88 112 -12 235 -12C266 -12 339 5 402 84L384 109ZM230 411C285 411 319 365 319 313C319 298 313 293 294 293C236 291 180 290 125 290C141 370 185 411 230 411Z" id="g58-99"></path><glyph.data ascent="1007" descent="-369" horiz-adv-x="434" vert-adv-y="434"></glyph.data></g><g transform="matrix(.0091,0,0,-0.0091,15.203,-5.872)"><path d="M303 37L293 66C280 59 256 49 231 49S173 63 173 143V396H281C294 404 298 428 287 439H173V575L158 577L92 509V439H46L17 408L22 396H92V107C92 27 128 -12 192 -12C203 -12 218 -9 237 2L303 37Z" id="g58-114"></path><glyph.data ascent="1007" descent="-369" horiz-adv-x="312" vert-adv-y="312"></glyph.data></g></svg> mice. (a) Female and (b) male NOD (filled circles) and NOD.<svg height="12.5011pt" id="M67" style="vertical-align:-0.2128992pt" version="1.1" viewbox="-0.0498162 -12.2882 35.0973 12.5011" width="35.0973pt" 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="M308 0V33C225 38 217 44 217 128V521C217 605 225 612 308 617V650H39V617C122 612 130 605 130 521V128C130 44 122 38 39 33V0H308Z" id="g58-71"></path><glyph.data ascent="1007" descent="-369" horiz-adv-x="348" vert-adv-y="348"></glyph.data></g><g transform="matrix(.013,0,0,-0.013,4.315,0)"><path d="M532 0V30C473 38 467 38 467 107V298C467 395 416 451 336 451C307 451 279 439 251 420C226 404 205 389 185 374V453C142 434 94 422 43 413V386C98 378 104 373 104 309V107C104 41 100 38 31 30V0H251V30C191 35 185 40 185 107V337C216 364 255 389 295 389C360 389 386 347 386 276V110C386 44 380 35 321 30V0H532Z" id="g58-108"></path><glyph.data ascent="1007" descent="-369" horiz-adv-x="557" vert-adv-y="557"></glyph.data></g><g transform="matrix(.013,0,0,-0.013,11.439,0)"><path d="M327 325C324 350 312 408 304 433C283 442 256 451 213 451C120 451 59 391 59 320C59 243 125 210 188 181C237 158 266 136 266 93C266 52 231 24 195 24C134 24 93 81 74 148L42 143C42 106 51 37 59 23C78 8 125 -12 177 -12C257 -12 345 35 345 127C345 198 292 234 216 264C171 283 131 305 131 348C131 387 156 416 195 416C243 416 277 378 297 317L327 325Z" id="g58-113"></path><glyph.data ascent="1007" descent="-369" horiz-adv-x="376" vert-adv-y="376"></glyph.data></g><g transform="matrix(.013,0,0,-0.013,16.327,0)"><path d="M414 144C384 79 371 75 317 75H135L276 221C367 316 408 376 408 465C408 570 327 635 237 635C179 635 131 609 100 575L42 494L67 471C94 510 138 565 205 565C277 565 321 517 321 435C321 348 258 270 195 195C146 137 88 81 33 26V0H411C423 44 433 88 446 135L414 144Z" id="g50-51"></path><glyph.data ascent="3443" descent="-2856" horiz-adv-x="487" vert-adv-y="487"></glyph.data></g><g transform="matrix(.0091,0,0,-0.0091,22.658,-5.872)"><path d="M522 0V30C462 35 455 41 455 106V280C455 397 397 451 314 451C262 451 206 414 171 379V710C131 698 69 682 20 675V647C87 642 90 637 90 574V106C90 41 80 35 20 30V0H236V30C176 35 171 43 171 106V339C198 371 237 391 276 391C341 391 374 350 374 269V106C374 43 367 35 308 30V0H522Z" id="g58-102"></path><glyph.data ascent="1007" descent="-369" horiz-adv-x="544" vert-adv-y="544"></glyph.data></g><g transform="matrix(.0091,0,0,-0.0091,27.581,-5.872)"><path d="M384 109C349 76 310 59 268 59C197 59 123 113 120 245C240 248 367 259 384 262C403 266 407 275 407 296C407 376 338 451 254 451H253C201 451 148 425 105 378C65 334 39 272 39 203C39 88 112 -12 235 -12C266 -12 339 5 402 84L384 109ZM230 411C285 411 319 365 319 313C319 298 313 293 294 293C236 291 180 290 125 290C141 370 185 411 230 411Z" id="g58-99"></path><glyph.data ascent="1007" descent="-369" horiz-adv-x="434" vert-adv-y="434"></glyph.data></g><g transform="matrix(.0091,0,0,-0.0091,31.53,-5.872)"><path d="M303 37L293 66C280 59 256 49 231 49S173 63 173 143V396H281C294 404 298 428 287 439H173V575L158 577L92 509V439H46L17 408L22 396H92V107C92 27 128 -12 192 -12C203 -12 218 -9 237 2L303 37Z" id="g58-114"></path><glyph.data ascent="1007" descent="-369" horiz-adv-x="312" vert-adv-y="312"></glyph.data></g></svg> mice (open circles) were followed weekly for diabetes development. (a) <svg height="11.6608pt" id="M68" style="vertical-align:-3.32502pt" version="1.1" viewbox="-0.0498162 -8.33578 45.37 11.6608" width="45.37pt" 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="M573 302C573 402 527 451 414 451C386 451 343 446 313 437L330 513L320 522C295 508 261 484 243 463L230 415C194 400 159 383 126 359L131 330C159 344 187 357 222 368L109 -147C96 -204 80 -214 18 -223L13 -255L256 -244L259 -212L236 -210C184 -205 180 -195 191 -141L219 -1C240 -10 268 -12 284 -12C352 4 431 48 484 104C543 166 573 240 573 302ZM481 290C481 165 381 37 305 37C280 37 249 56 235 71L302 395C328 399 353 402 372 402C427 402 481 378 481 290Z" id="g50-113"></path><glyph.data ascent="3443" descent="-2856" horiz-adv-x="597" vert-adv-y="597"></glyph.data></g><g transform="matrix(.013,0,0,-0.013,11.438,0)"><path d="M556 331V384H55V331H556ZM556 140V193H55V140H556Z" id="g54-34"></path><glyph.data ascent="3443" descent="-2856" horiz-adv-x="611" vert-adv-y="611"></glyph.data></g><g transform="matrix(.013,0,0,-0.013,23.056,0)"><path d="M245 635C92 635 37 457 37 312C37 149 91 -12 244 -12C395 -12 449 166 449 312C449 469 395 635 245 635ZM243 598C332 598 358 454 358 312C358 173 334 26 245 26C158 26 128 174 128 313S152 598 243 598Z" id="g50-49"></path><glyph.data ascent="3443" descent="-2856" horiz-adv-x="487" vert-adv-y="487"></glyph.data></g><g transform="matrix(.013,0,0,-0.013,29.387,0)"><path d="M117 -12C153 -12 178 12 178 50C178 84 153 110 118 110C84 110 59 84 59 50C59 12 84 -12 117 -12Z" id="g50-47"></path><glyph.data ascent="3443" descent="-2856" horiz-adv-x="237" vert-adv-y="237"></glyph.data></g><g transform="matrix(.013,0,0,-0.013,32.468,0)"><path d="M141 347C171 480 264 541 327 570C364 587 403 599 436 605L429 641C389 634 339 622 300 609C191 570 37 458 37 239C37 86 126 -12 245 -12C367 -12 454 89 454 210C454 314 380 397 272 397C252 397 230 390 208 380L141 347ZM231 338C323 338 366 257 366 174C366 108 340 27 263 27C180 27 129 123 129 244C129 268 130 292 135 310C158 323 193 338 231 338Z" id="g50-55"></path><glyph.data ascent="3443" descent="-2856" horiz-adv-x="487" vert-adv-y="487"></glyph.data></g><g transform="matrix(.013,0,0,-0.013,38.799,0)"><path d="M290 377C321 398 342 415 358 430C378 450 389 473 389 502C389 578 329 635 238 635H237C184 635 137 610 109 578L64 515L88 493C112 529 154 573 208 573S303 542 303 482C303 409 233 370 141 341L149 308C165 313 190 319 215 319C272 319 341 283 341 193C342 98 292 43 222 43C163 43 122 72 96 94C88 101 79 100 70 94C61 87 47 73 46 60C44 47 48 37 62 23C76 10 118 -12 165 -12C238 -12 430 62 430 223C430 297 379 359 290 375V377Z" id="g50-52"></path><glyph.data ascent="3443" descent="-2856" horiz-adv-x="487" vert-adv-y="487"></glyph.data></g></svg> (not significant), Mantel-Cox. (b) <svg height="11.6608pt" id="M69" style="vertical-align:-3.32502pt" version="1.1" viewbox="-0.0498162 -8.33578 45.37 11.6608" width="45.37pt" 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="M573 302C573 402 527 451 414 451C386 451 343 446 313 437L330 513L320 522C295 508 261 484 243 463L230 415C194 400 159 383 126 359L131 330C159 344 187 357 222 368L109 -147C96 -204 80 -214 18 -223L13 -255L256 -244L259 -212L236 -210C184 -205 180 -195 191 -141L219 -1C240 -10 268 -12 284 -12C352 4 431 48 484 104C543 166 573 240 573 302ZM481 290C481 165 381 37 305 37C280 37 249 56 235 71L302 395C328 399 353 402 372 402C427 402 481 378 481 290Z" id="g50-113"></path><glyph.data ascent="3443" descent="-2856" horiz-adv-x="597" vert-adv-y="597"></glyph.data></g><g transform="matrix(.013,0,0,-0.013,11.438,0)"><path d="M556 331V384H55V331H556ZM556 140V193H55V140H556Z" id="g54-34"></path><glyph.data ascent="3443" descent="-2856" horiz-adv-x="611" vert-adv-y="611"></glyph.data></g><g transform="matrix(.013,0,0,-0.013,23.056,0)"><path d="M245 635C92 635 37 457 37 312C37 149 91 -12 244 -12C395 -12 449 166 449 312C449 469 395 635 245 635ZM243 598C332 598 358 454 358 312C358 173 334 26 245 26C158 26 128 174 128 313S152 598 243 598Z" id="g50-49"></path><glyph.data ascent="3443" descent="-2856" horiz-adv-x="487" vert-adv-y="487"></glyph.data></g><g transform="matrix(.013,0,0,-0.013,29.387,0)"><path d="M117 -12C153 -12 178 12 178 50C178 84 153 110 118 110C84 110 59 84 59 50C59 12 84 -12 117 -12Z" id="g50-47"></path><glyph.data ascent="3443" descent="-2856" horiz-adv-x="237" vert-adv-y="237"></glyph.data></g><g transform="matrix(.013,0,0,-0.013,32.468,0)"><path d="M389 0V32C297 38 291 46 291 118V635C234 613 175 595 109 583V556L161 554C203 552 207 547 207 497V118C207 46 201 38 110 32V0H389Z" id="g50-50"></path><glyph.data ascent="3443" descent="-2856" horiz-adv-x="487" vert-adv-y="487"></glyph.data></g><g transform="matrix(.013,0,0,-0.013,38.799,0)"><path d="M247 635C116 635 39 518 39 421C39 315 113 237 221 237C239 237 258 241 281 253L349 289C315 140 204 42 60 19L66 -15C90 -15 153 -5 207 16C344 70 447 199 447 385C447 521 373 635 247 635ZM231 598C329 598 356 478 356 390C356 371 355 347 352 325C330 309 297 297 262 297C179 297 127 369 127 456C127 515 156 598 231 598Z" id="g50-58"></path><glyph.data ascent="3443" descent="-2856" horiz-adv-x="487" vert-adv-y="487"></glyph.data></g></svg> (not significant), Mantel-Cox.</div>

Journal of Diabetes Research

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Figure 2

Figure 2: An HLA-Transgenic Mouse Model of Type 1 Diabetes That Incorporates the Reduced but Not Abolished Thymic Insulin Expression Seen in Patients 

Figure 2 | An HLA-Transgenic Mouse Model of Type 1 Diabetes That Incorporates the Reduced but Not Abolished Thymic Insulin Expression Seen in Patients 