Gene targeting of Desrt, a novel ARID class DNA-binding protein, causes growth retardation and abnormal development of reproductive organs.
We have cloned and characterized a novel murine DNA-binding protein Desrt, with a motif characteristic of the ARID (A-T rich interaction domain) family of transcription factors. The Desrt gene encodes an 83-kD protein that is shown to bind DNA and is widely expressed in adult tissues. To examine the in vivo function of Desrt, we have generated mice with a targeted mutation in the ARID domain of Desrt. Homozygous mutants have reduced viability, pronounced growth retardation, and a high incidence of abnormalities of the female and male reproductive organs including cryptorchidism. This may thus serve as a model to dissect the mechanisms involved in the development of the reproductive tract including testicular descent. Gene-targeted mice also display a reduction in the thickness of the zona reticularis of the adrenal gland and transient aberrations of the T and B cell compartments of primary lymphoid organs. These data show that this novel DNA-binding protein, Desrt, has a nonredundant function during growth and in the development of the reproductive system.
Lahoud
M H
MH
Centre for Functional Genomics and Human Disease, Monash Institute of Reproduction and Development, Monash University, Melbourne, Victoria, Australia.
Ristevski
S
S
Venter
D J
DJ
Jermiin
L S
LS
Bertoncello
I
I
Zavarsek
S
S
Hasthorpe
S
S
Drago
J
J
de Kretser
D
D
Hertzog
P J
PJ
Kola
I
I
D020856:AT Rich Sequence / Q000235:genetics; D000311:Adrenal Glands / Q000002:abnormalities; D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D001483:Base Sequence / Q000235:genetics; D001665:Binding Sites / Q000235:genetics; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics*; D005260:Female; D018390:Gene Targeting / Q000379:methods*; D005836:Genitalia, Female / Q000002:abnormalities* / Q000254:growth & development*; D005837:Genitalia, Male / Q000002:abnormalities* / Q000254:growth & development*; D006130:Growth Disorders / Q000235:genetics*; D006801:Humans; D007107:Immune System / Q000002:abnormalities; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010446:Peptide Fragments / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics*
D004268:DNA-Binding Proteins; C434825:Desrt protein, mouse; D010446:Peptide Fragments; D014157:Transcription Factors