Cloning of inv, a gene that controls left/right asymmetry and kidney development.
Most vertebrate internal organs show a distinctive left/right asymmetry. The inv (inversion of embryonic turning) mutation in mice was created previously by random insertional mutagenesis; it produces both a constant reversal of left/right polarity (situs inversus) and cyst formation in the kidneys. Asymmetric expression patterns of the genes nodal and lefty are reversed in the inv mutant, indicating that inv may act early in left/right determination. Here we identify a new gene located at the inv locus. The encoded protein contains 15 consecutive repeats of an Ank/Swi6 motif at its amino terminus. Expression of the gene is the highest in the kidneys and liver among adult tissues, and is seen in presomite-stage embryos. Analysis of the transgenic genome and the structure of the candidate gene indicate that the candidate gene is the only gene that is disrupted in inv mutants. Transgenic introduction of a minigene encoding the candidate protein restores normal left/right asymmetry and kidney development in the inv mutant, confirming the identity of the candidate gene.
Mochizuki
T
T
Department of Medicine, Kidney Center, Tokyo Women's Medical University, School of Medicine, Japan.
Saijoh
Y
Y
Tsuchiya
K
K
Shirayoshi
Y
Y
Takai
S
S
Taya
C
C
Yonekawa
H
H
Yamada
K
K
Nihei
H
H
Nakatsuji
N
N
Overbeek
P A
PA
Hamada
H
H
Yokoyama
T
T
D000595:Amino Acid Sequence; D000818:Animals; D017089:Ankyrin Repeat; D015152:Blotting, Northern; D015139:Blotting, Southern; D019521:Body Patterning / Q000235:genetics*; D018244:Chromosomes, Artificial, Yeast; D003001:Cloning, Molecular; D005260:Female; D007668:Kidney / Q000196:embryology* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D011506:Proteins / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors
C491947:Invs protein, mouse; D011506:Proteins; D014157:Transcription Factors