PMID- 22502604 OWN - NLM STAT- MEDLINE DCOM- 20120823 LR - 20211203 IS - 1873-2747 (Electronic) IS - 0361-9230 (Linking) VI - 88 IP - 1 DP - 2012 May 1 TI - Mouse models of neuronal ceroid lipofuscinoses: useful pre-clinical tools to delineate disease pathophysiology and validate therapeutics. PG - 43-57 LID - 10.1016/j.brainresbull.2012.03.003 [doi] AB - The neuronal ceroid lipofuscinoses (NCL, also known as Batten disease) is a devastating neurodegenerative diseases caused by mutations in either soluble enzymes or membrane-associated structural proteins that result in lysosome dysfunction. Different forms of NCL were defined initially by age of onset, affected population and/or type of storage material but collectively represent the most prevalent pediatric hereditary neurovisceral storage disorder. Specific gene mutations are now known for each subclass of NCL in humans that now largely define the disease: cathepsin D (CTSD) for congenital (CLN10 form); palmitoyl protein thioesterase 1 (PPT1) for infantile (CLN1 form); tripeptidyl peptidase 1 (TPP1) for classic late infantile (CLN2 form); variant late infantile-CLN5, CLN6 or CLN8 for variant late infantile forms; and CLN3 for juvenile (CLN3 form). Several mouse models of NCL have been developed, or in some cases exist sporadically, that exhibit mutations producing a progressive neurodegenerative phenotype similar to that observed in human NCL. The study of these mouse models of NCL has dramatically advanced our knowledge of NCL pathophysiology and in some cases has helped delineate the function of proteins mutated in human NCL. In addition, NCL mutant mice have been tested for several different therapeutic approaches and as such they have become important pre-clinical models for validating treatment options. In this review we will assess the current state of mouse models of NCL with regards to their unique pathophysiology and how these mice have helped investigators achieve a better understanding of human NCL disease and therapy. CI - Published by Elsevier Inc. FAU - Shacka, John J AU - Shacka JJ AD - Neuropathology Division, Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA. shacka@uab.edu LA - eng GR - P30 NS47466/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, U.S. Gov't, Non-P.H.S. PT - Review DEP - 20120328 PL - United States TA - Brain Res Bull JT - Brain research bulletin JID - 7605818 SB - IM MH - Animals MH - *Disease Models, Animal MH - Humans MH - Mice MH - *Mice, Neurologic Mutants MH - Neuronal Ceroid-Lipofuscinoses/*genetics/*physiopathology MH - Tripeptidyl-Peptidase 1 EDAT- 2012/04/17 06:00 MHDA- 2012/08/24 06:00 CRDT- 2012/04/17 06:00 PHST- 2011/07/18 00:00 [received] PHST- 2012/03/04 00:00 [revised] PHST- 2012/03/14 00:00 [accepted] PHST- 2012/04/17 06:00 [entrez] PHST- 2012/04/17 06:00 [pubmed] PHST- 2012/08/24 06:00 [medline] AID - S0361-9230(12)00046-9 [pii] AID - 10.1016/j.brainresbull.2012.03.003 [doi] PST - ppublish SO - Brain Res Bull. 2012 May 1;88(1):43-57. doi: 10.1016/j.brainresbull.2012.03.003. Epub 2012 Mar 28.