Endpoints in myelin-deficient (MD) rats.
Health problems in some animal models remain unexplained, rendering in vivo studies ethically challenging, especially when experimental animals are prone to sudden death. Over the last 3 decades, the myelin-deficient (md) rat, a strain with severe dysmyelination due to mutant proteolipid protein, has been key to important discoveries in mechanisms of myelination and glial cell biology. The usefulness of this mutant rat, however, has been limited by sudden death during the fourth week of life. Timely euthanasia has been difficult because the cause of these mortalities remains unexplained and the endpoint not determined. In this clinicopathologic study, we determined that sudden onset of hindlimb paralysis inevitably leads to paralysis of the urinary bladder and then breathing difficulties because of severe injury to the spinal cord in the midthoracic region with concurrent narrowing of the vertebral canal due to fracture of a vertebral body. Sudden onset of hindlimb paralysis likely is related to seizures and severe muscle spasms that begin to occur at the end of the third week of life. Once seizure activity begins, we recommend frequent monitoring of md rats for hindlimb paralysis and distention of the urinary bladder as indication of endpoints mandating prompt euthanasia.
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada. Kwiecien@mcmaster.ca
Jacek M
JM
Kwiecien
Kathleen H
KH
Delaney
D000827:Animal Welfare; D000818:Animals; D002423:Cause of Death; D003645:Death, Sudden / Q000473:pathology / Q000662:veterinary*; D004195:Disease Models, Animal; D023381:Endpoint Determination; D037901:Euthanasia, Animal; D005260:Female; D006579:Heterozygote; D008297:Male; D018991:Myelin Proteolipid Protein / Q000235:genetics*; D010243:Paralysis / Q000473:pathology / Q000662:veterinary; D051381:Rats / Q000235:genetics*; D017208:Rats, Wistar; D012640:Seizures / Q000473:pathology / Q000662:veterinary; D013997:Time Factors
D018991:Myelin Proteolipid Protein
J Comp Neurol. 2002 Apr 22;446(1):46-57
11920719
Exp Neurol. 1997 Sep;147(1):84-95
9294405
Neuroimage. 2009 Oct 15;48(1):109-16
19539038
Am J Pathol. 1979 Apr;95(1):215-24
434110
J Neurosci. 2002 Mar 1;22(5):1726-37
11880502
J Neurocytol. 1998 Aug;27(8):581-91
10405025
J Neurosci Res. 1998 Dec 1;54(5):623-34
9843153
Ann Neurol. 1999 Nov;46(5):716-22
10553988
Comp Med. 2010 Jun;60(3):205-17
20579436
J Neuroimmunol. 1998 May 15;85(2):202-11
9630169
J Neurocytol. 1988 Oct;17(5):657-70
3210045
J Neurosci. 2003 Mar 15;23(6):2265-73
12657685
Neurochem Res. 1999 Feb;24(2):235-48
9972870
J Neurocytol. 1995 Sep;24(9):654-66
7500121
Dev Biol. 1993 Jun;157(2):334-47
8500648
Lab Anim Sci. 1995 Oct;45(5):547-53
8569154
Magn Reson Imaging. 2006 Feb;24(2):161-6
16455404
Exp Neurol. 2005 Jun;193(2):334-49
15869936
J Neurol Sci. 1992 Jan;107(1):78-86
1578238
J Neurosci Res. 1997 Dec 1;50(5):872-87
9418974
Hear Res. 2004 May;191(1-2):119-24
15109711
J Comp Neurol. 1998 Sep 14;399(1):94-100
9725703
Proc Natl Acad Sci U S A. 1987 Sep;84(17):6287-91
3476944
Respir Physiol Neurobiol. 2009 Dec 31;169(3):303-14
19808102
J Neurochem. 1986 Dec;47(6):1901-7
2430065
J Neurochem. 1990 Mar;54(3):1079-81
1689377
Comp Med. 2000 Oct;50(5):503-10
11099133
J Comp Neurol. 1997 Feb 3;378(1):105-16
9120050
J Neurosci Res. 1998 Feb 15;51(4):497-507
9514203
J Neurosci Res. 1997 Feb 1;47(3):264-70
9039648
J Neurosci Res. 2001 May 15;64(4):371-9
11340644
J Neurocytol. 1995 Oct;24(10):745-62
8586995
Nature. 1997 Apr 17;386(6626):724-8
9109490