EMBRYONIC LETHALITY IN MICE HOMOZYGOUS FOR A TARGETED DISRUPTION OF THE N-MYC GENE

被引:276
作者
CHARRON, J
MALYNN, BA
FISHER, P
STEWART, V
JEANNOTTE, L
GOFF, SP
ROBERTSON, EJ
ALT, FW
机构
[1] COLUMBIA UNIV COLL PHYS & SURG, DEPT MICROBIOL, NEW YORK, NY 10032 USA
[2] COLUMBIA UNIV COLL PHYS & SURG, DEPT BIOCHEM & MOLEC BIOPHYS, NEW YORK, NY 10032 USA
[3] UNIV LAVAL, HOTEL DIEU, CTR RECH CANCEROL, QUEBEC CITY G1R 2J6, QUEBEC, CANADA
[4] CHILDRENS HOSP MED CTR, HOWARD HUGHES MED INST, BOSTON, MA 02115 USA
[5] COLUMBIA UNIV COLL PHYS & SURG, DEPT PATHOL, NEW YORK, NY 10032 USA
[6] COLUMBIA UNIV COLL PHYS & SURG, DEPT GENET & DEV, NEW YORK, NY 10032 USA
关键词
GENE DISRUPTION; N-MYC; DEVELOPMENTAL RETARDATION;
D O I
10.1101/gad.6.12a.2248
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The N-myc gene encodes a putative transcription factor that is thought to function in the regulation of gene expression during cell differentiation and/or growth. To examine the role of N-myc during development, we have used targeted mutagenesis in embryonic stem cells to produce a mouse line that carries an N-myc null allele. Mice homozygous for the mutation died between 10.5 and 12.5 days of gestation. Histological analysis of mutant embryos revealed that organs and tissues expected at these stages of development were present. However, multiple defects were observed, primarily in tissues and organs that normally express N-myc. In particular, mutant hearts were underdeveloped, often retaining the S-shape more typical of 9-day-old embryos. In addition, cranial and spinal ganglia were reduced in size and/or cellularity. Most of the noted defects were more consistent with a role of N-myc in proliferation of precursor populations than with a block in differentiation per se, at least at these early stages. These results demonstrate that N-myc plays an essential role during development and clearly confirm that N-myc has a physiological function that is distinct from that of the other myc-family genes.
引用
收藏
页码:2248 / 2257
页数:10
相关论文
共 59 条
[1]   DETERMINATION OF THE DNA-SEQUENCE RECOGNIZED BY THE BHLH-ZIP DOMAIN OF THE N-MYC PROTEIN [J].
ALEX, R ;
SOZERI, O ;
MEYER, S ;
DILDROP, R .
NUCLEIC ACIDS RESEARCH, 1992, 20 (09) :2257-2263
[2]   THE HUMAN MYC GENE FAMILY [J].
ALT, FW ;
DEPINHO, R ;
ZIMMERMAN, K ;
LEGOUY, E ;
HATTON, K ;
FERRIER, P ;
TESFAYE, A ;
YANCOPOULOS, G ;
NISEN, P .
COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY, 1986, 51 :931-941
[3]  
Altman J., 1982, DEV CRANIAL NERVE GA
[4]  
AUFFRAY C, 1980, EUR J BIOCHEM, V107, P303
[5]  
BERNELOTMOENS C, 1992, GENE DEV, V6, P691
[6]   SEQUENCE-SPECIFIC DNA-BINDING BY THE C-MYC PROTEIN [J].
BLACKWELL, TK ;
KRETZNER, L ;
BLACKWOOD, EM ;
EISENMAN, RN ;
WEINTRAUB, H .
SCIENCE, 1990, 250 (4984) :1149-1151
[7]   MAX - A HELIX-LOOP-HELIX ZIPPER PROTEIN THAT FORMS A SEQUENCE-SPECIFIC DNA-BINDING COMPLEX WITH MYC [J].
BLACKWOOD, EM ;
EISENMAN, RN .
SCIENCE, 1991, 251 (4998) :1211-1217
[8]   DAUGHTERLESS, A DROSOPHILA GENE ESSENTIAL FOR BOTH NEUROGENESIS AND SEX DETERMINATION, HAS SEQUENCE SIMILARITIES TO MYC AND THE ACHAETE-SCUTE COMPLEX [J].
CAUDY, M ;
VASSIN, H ;
BRAND, M ;
TUMA, R ;
JAN, LY ;
JAN, YN .
CELL, 1988, 55 (06) :1061-1067
[9]  
CAVALIERI F, 1988, ONCOGENE, V2, P289
[10]   HIGH-FREQUENCY DISRUPTION OF THE N-MYC GENE IN EMBRYONIC STEM AND PRE-B-CELL LINES BY HOMOLOGOUS RECOMBINATION [J].
CHARRON, J ;
MALYNN, BA ;
ROBERTSON, EJ ;
GOFF, SP ;
ALT, FW .
MOLECULAR AND CELLULAR BIOLOGY, 1990, 10 (04) :1799-1804