We studied the fate of skeletal muscle obtained from patients with amy- otrophic lateral sclerosis zyxwv (ALS) after transplantation into immunodeficient nude mice. The transplanted muscle consistently survived in the nude mice without immunological rejection. The myofibers in these muscles underwent degeneration, followed by regeneration, maturation, and eventual functional innervationby the mouse motor neurons. The ability to grow diseased human muscle successfully over a prolonged period in nude mice offers an in vivo model to study the etiology of ALS and possibly of other neuromuscular disorders. MUSCLE & NERVE 1133-38 1988 GROWTH OF SKELETAL MUSCLE FROM PATIENTS WITH AMYOTROPHIC LATERAL SCLEROSIS TRANSPLANTED INTO NUDE MICE ADARSH K. GULATI, PhD, MICHAEL H. RIVNER, MD, MORTEZA SHAMSNIA, MD, THOMAS R. SWIFT, MD, and GURKIRPAL S. SOHAL, PhD zyxwvuts Aniyotrop1iic. lateral sclerosis zyxwvuts (AM) is ;i tiisease characterized by atrophy of skelelal muscle owii tg to degeneration and loss of both lower arid upper niotor neurons in the central net-vous system.".' 'llie etiology of this Ikil disease is unknown, id- though several causative factors have been p1.0- posed. 'l'hese iriclutle viral infec~ion;'.l' toxicity with heavy ")et&;~.l~.y~ presence of huiiioi-al ininiuiie factors arid circulating toxins; "wl I- <tc zyxwvuts .li ( 11' llelll-o- trophic factor(s)corning f'rom skeletal muscle, atid factors related to traumatic damage of muscle; I"" and otIiers.:'.'" 'I'tie lack of' rrtitlerstancling of' the cause of A1.S as well as of' other tieiirotiiiiscLi1;II. diseases is partly attrilmted to the unavailal)ility of' a 1) pro pria te ex pe rim e 11 t al I I I( XI zyxwvutsrqponml e Is 1Oi. s u c t i c 1 is - eases. 15.22 111 ;in attempt to develop such ;I iiiotlel we tIaiisplantec1 skeletal muscle obcaiiictl ['ro~ii pi- tierits with ALS into immunocleficierit nutlc riiice. From the Departments ot Anatomy (Drs Gulati and Sonal) and Neurolcigy (Drs Rivner Shamsnia, and Swift) Medical College of Georgia Augbita GA Acknowledgments The authors thank Dr Dale E Bockman tor helpful discussions and comments, Jill Trelz and Brenda Headrick for galudble technical assistance, and Sandra Dunn and Tanda Moffit for skillful prep aration of the manuscript Address reprint request to Dr Guldli at Ihe Departnient of Anatomy Med ical College of Georgia Augusta GA 3091 2 Received for publication June 30. 1986 revised manuscript acceptea lor publication December 10, 1986 * 1988 John Wiley & Sons Inc 0148-639X/1100/0033 $04 zyxwvutsrqpo 0016 We IY~OI t liere ttiat huiiian iriuscle I ernairis vidde, witlet-goes regeiieration, and beconies rciriner- vatetl af tei- tratisplanatioii. A preliminary report of t hi\ wot-k has lieen published elsewhere in ihtt-act fi)riii ." MATERIALS AND METHODS Six to eight-week old male nucle mice (nu AF) 01)- tiiitietl I'roni tlarhri Spi~gue. 1)awle) Inc. (I titli- aiiiipolis, IN) set.\,etl as recipients of'huriim Iiiiisck. Muscle simples were 1.emovct1 f'rom 5 patients (4 years) cliagiiosetl as having ALS I~asetl on cliiiical, histological, arid iicurophysiologic~il evaluations. All paticnts give inl'oriiied comerit pi-iot. to niiiscle re- ~iioval. Llndei. local anesthesia ;i tliopsy of'the Iiiceps iiiuscle wiis perfimned, aiid ;I cylindrical piece of niuscle tl-5 inm in tlianieter arid ti-8 nini in length \v;is ol)taiiied. 'I'tie tiiusck tissue was itnnicdiately placed iii tissue culture tiietliuni (a-MEM, C;it)co I,al)s, (;i.aiid Islaiid, NP') aritl divided into pieces 1.5-2.0 nini in tlianieter mcl 6-7 inin in leiigtli. One such piece was 1'1-ozen in liquid nitrogen for nior~~liolo~ic~il arialysis, whereas others were trans- planted into Iiutle mice. ~l'he muscle traiisplmta- tioti pt-occdure w;is ;idaptctl I'rom that iisetl ill our earlier. st~idies.~~"' 'I'tie recipient nude nioiise was anestherizecl with chloral hydrate (4 mg/I 0 g body weight, i.p.), and its extensor tligitoi-uni longus (FBL) niuscle was exposed atid reniovetl by cuttiiig both nlell allti 1 wonlall, ages rallgeti ft-om 50 to 70 Human Muscle Growth in Nude Mice MUSCLE & NERVE January 1988 33