Mice deficient in the ALS2 gene exhibit lymphopenia and abnormal hematopietic function

被引：7

作者：

Erie, Elizabeth A.

Shim, Hoon

Smith, Aleah L.

Lin, Xian

Keyvanfar, Keyvan

Xie, Chengsong

Chen, Jichun

Cai, Huaibin

机构：

[1] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA

[2] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA

来源：

JOURNAL OF NEUROIMMUNOLOGY | 2007年 / 182卷 / 1-2期

关键词：

amyotrophic lateral sclerosis (ALS); ALS2; ALS2 knockout mice; lymphopenia; hematopoietic stem and progenitor cells; cytokine-stimulated proliferation;

D O I：

10.1016/j.jneuroim.2006.10.019

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

One form of juvenile onset autosomal recessive amyotrophic lateral sclerosis (ALS2) has been linked to the dysfunction of the ALS2 gene. The ALS2 gene is expressed in lymphoblasts, however, whether ALS2-deficiency affects periphery blood is unclear. Here we report that ALS2 knockout (ALS2(-/-)) mice developed peripheral lymphopenia but had higher proportions of hematopoietic stem and progenitor cells in which the stem cell factor-induced cell proliferation was up-regulated. Our findings reveal a novel function of the ALS2 gene in the lymphopoicsis and hernatopoiesis, suggesting that the immune system is involved in the pathogenesis of ALS2. (c) 2006 Elsevier B.V. All rights reserved.

引用

收藏

页码：226 / 231

页数：6

相关论文

共 24 条

[1] Loss of ALS2 function is insufficient to trigger motor neuron degeneration in knock-out mice but predisposes neurons to oxidative stress [J].

Cai, HB ;

Lin, X ;

Xie, CS ;

Laird, FM ;

Lai, C ;

Wen, HJ ;

Chiang, HC ;

Shim, H ;

Farah, MH ;

Hoke, A ;

Price, DL ;

Wong, PC .

JOURNAL OF NEUROSCIENCE, 2005, 25 (33) :7567-7574

[2] Rac GTPases differentially integrate signals regulating hematopoietic stem cell localization [J].

Cancelas, JA ;

Lee, AW ;

Prabhakar, R ;

Stringer, KF ;

Zheng, Y ;

Williams, DA .

NATURE MEDICINE, 2005, 11 (08) :886-891

[3] Hematopoietic stem cell functional failure in interleukin-2-deficient mice [J].

Chen, J ;

Astle, CM ;

Harrison, DE .

JOURNAL OF HEMATOTHERAPY & STEM CELL RESEARCH, 2002, 11 (06) :905-912

[4] From Charcot to Lou Gehrig: Deciphering selective motor neuron death in ALS [J].

Cleveland, DW ;

Rothstein, JD .

NATURE REVIEWS NEUROSCIENCE, 2001, 2 (11) :806-819

[5] Als2-deficient mice exhibit disturbances in endosome trafficking associated with motor behavioral abnormalities [J].

Devon, R. S. ;

Orban, P. C. ;

Gerrow, K. ;

Barbieri, M. A. ;

Schwab, C. ;

Cao, L. P. ;

Helm, J. R. ;

Bissada, N. ;

Cruz-Aguado, R. ;

Davidson, T. -L. ;

Witmer, J. ;

Metzler, M. ;

Lam, C. K. ;

Tetzlaff, W. ;

Simpson, E. M. ;

McCaffery, J. M. ;

El-Husseini, A. E. ;

Leavitt, B. R. ;

Hayden, M. R. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (25) :9595-9600

[6] Role of the monomeric GTPase Rho in hematopoietic progenitor cell migration and transplantation [J].

Göttig, S ;

Möbest, D ;

Rüster, B ;

Grace, B ;

Winter, S ;

Seifried, E ;

Gille, J ;

Wieland, T ;

Henschler, R .

EUROPEAN JOURNAL OF IMMUNOLOGY, 2006, 36 (01) :180-189

[7] Mice deficient in the Rab5 guanine nucleotide exchange factor ALS2/alsin exhibit age-dependent neurological deficits and altered endosome trafficking [J].

Hadano, S ;

Benn, SC ;

Kakuta, S ;

Otomo, A ;

Sudo, K ;

Kunita, R ;

Suzuki-Utsunomiya, K ;

Mizumura, H ;

Shefner, JM ;

Cox, GA ;

Iwakura, Y ;

Brown, RH ;

Ikeda, JE .

HUMAN MOLECULAR GENETICS, 2006, 15 (02) :233-250

[8] A gene encoding a putative GTPase regulator is mutated in familial amyotrophic lateral sclerosis 2 [J].

Hadano, S ;

Hand, CK ;

Osuga, H ;

Yanagisawa, Y ;

Otomo, A ;

Devon, RS ;

Miyamoto, N ;

Showguchi-Miyata, J ;

Okada, Y ;

Singaraja, R ;

Figlewicz, DA ;

Kwiatkowski, T ;

Hosler, BA ;

Sagie, T ;

Skaug, J ;

Nasir, J ;

Brown, RH ;

Scherer, SW ;

Rouleau, GA ;

Hayden, MR ;

Ikeda, JE .

NATURE GENETICS, 2001, 29 (02) :166-173

[9] The effect of pressure drop on respirator faceseal leakage [J].

Janssen, L ;

Weber, R .

JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL HYGIENE, 2005, 2 (07) :335-340

[10] Lymphopenia and spontaneous autorosette formation in SOD1 mouse model of ALS [J].

Kuzmenok, OI ;

Sanberg, PR ;

Desjarlais, TG ;

Bennett, SP ;

Garbuzova-Davis, SN .

JOURNAL OF NEUROIMMUNOLOGY, 2006, 172 (1-2) :132-136