Early changes in gene expression in two models of Batten disease.
Infantile and juvenile neuronal ceroid lipofuscinosis (NCLs) are progressive neurodegenerative disorders of childhood with distinct ages of clinical onset, but with a similar pathological outcome. Infantile and juvenile NCL are inherited in an autosomal recessive manner due to mutations in the CLN1 and CLN3 genes, respectively. Recently developed Cln1- and Cln3-knockout mouse models share similarities in pathology with the respective human disease. Using oligonucleotide arrays we identified reproducible changes in gene expression in the brains of both 10-week-old Cln1- and Cln3-knockout mice as compared to wild-type controls, and confirmed changes in levels of several of the cognate proteins by immunoblotting. Despite the similarities in pathology, the two mutations affect the expression of different, non-overlapping sets of genes. The possible significance of these changes and the pathological mechanisms underlying NCL diseases are discussed.
Elshatory
Yasser
Y
Center for Aging and Developmental Biology, University of Rochester School of Medicine and Dentistry, University of Rochester, Rochester, NY 14642, USA.
Brooks
Andrew I
AI
Chattopadhyay
Subrata
S
Curran
Timothy M
TM
Gupta
Praveena
P
Ramalingam
Vijay
V
Hofmann
Sandra L
SL
Pearce
David A
DA
D000818:Animals; D001921:Brain / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D018832:Molecular Chaperones; D009472:Neuronal Ceroid-Lipofuscinoses / Q000235:genetics*; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D013869:Thiolester Hydrolases
C105199:CLN3 protein, human; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D018832:Molecular Chaperones; D011506:Proteins; D013869:Thiolester Hydrolases; C416054:PPT1 protein, human