TITLE

Insertion of Inhbb into the Inhba locus rescues the Inhba-null phenotype and reveals new activin functions

AUTHOR(S)

Brown, Chester W.; Houston-Hawkins, Dianne E.; Woodruff, Teresa K.; Matzuk, Martin M.

PUB. DATE

August 2000

SOURCE

Nature Genetics;Aug2000, Vol. 25 Issue 4, p453

SOURCE TYPE

Academic Journal

DOC. TYPE

Article

ABSTRACT

The activins (dimers of �A or �B subunits, encoded by the genes Inhba and Inhbb, respectively) are TGF-� superfamily members that have roles in reproduction and development. Whereas mice homozygous for the Inhba-null allele demonstrate disruption of whisker, palate and tooth development, leading to neonatal lethality, homozygous Inhbb-null mice are viable, fertile and have eye defects. To determine if these phenotypes were due to spatiotemporal expression differences of the ligands or disruption of specific ligand-receptor interactions, we replaced the region of Inhba encoding the mature protein with Inhbb, creating the allele Inhba[sup tm2Zuk] (hereafter designated Inhba[sub BK]). Although the craniofacial phenotypes of the Inhba-null mutation were rescued by the Inhba[sub BK] allele, somatic, testicular, genital and hair growth were grossly affected and influenced by the dosage and bioactivity of the allele. Thus, functional compensation within the TGF-� superfamily can occur if the replacement gene is expressed appropriately. The novel phenotypes in these mice further illustrate the usefulness of insertion strategies for defining protein function.

ACCESSION #

8815494

Tags: ACTIVIN;  PHENOTYPE

 

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