title: Defective skeletogenesis with kidney stone formation in dwarf zebrafish mutant for trpm7.
abstract: Development of the adult form requires coordinated growth and patterning of multiple traits in response to local gene activity as well as to global endocrine and physiological effectors. An excellent example of such coordination is the skeleton. Skeletal development depends on the differentiation and morphogenesis of multiple cell types to generate elements with distinct forms and functions throughout the body. We show that zebrafish touchtone/nutria mutants exhibit severe growth retardation and gross alterations in skeletal development in addition to embryonic melanophore and touch-response defects. These alterations include accelerated endochondral ossification but delayed intramembranous ossification, as well as skeletal deformities. We show that the touchtone/nutria phenotype results from mutations in trpm7, which encodes a transient receptor potential (TRP) family member that functions as both a cation channel and kinase. We find trpm7 expression in the mesonephric kidney and show that mutants develop kidney stones, indicating renal dysfunction. These results identify a requirement for trpm7 in growth and skeletogenesis and highlight the potential of forward genetic approaches to uncover physiological mechanisms contributing to the development of adult form.
authors.affiliation: Section of Integrative Biology, Institute for Cellular and Molecular Biology, University of Texas at Austin, 1 University Station C0930, Austin, Texas 78712, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Elizondo
authors.forename: Brigitte L
authors.initials: BL
authors.lastname: Arduini
authors.forename: Jennifer
authors.initials: J
authors.lastname: Paulsen
authors.forename: Erin L
authors.initials: EL
authors.lastname: MacDonald
authors.forename: Jaime L
authors.initials: JL
authors.lastname: Sabel
authors.forename: Paul D
authors.initials: PD
authors.lastname: Henion
authors.forename: Robert A
authors.initials: RA
authors.lastname: Cornell
authors.forename: David M
authors.initials: DM
authors.lastname: Parichy
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D001842:Bone and Bones / Q000033:anatomy & histology; D002874:Chromosome Mapping; D018076:DNA, Complementary / Q000235:genetics; D006652:Histological Techniques; D017403:In Situ Hybridization; D007473:Ion Channels / Q000235:genetics* / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D007669:Kidney Calculi / Q000235:genetics / Q000662:veterinary*; D007814:Larva / Q000378:metabolism; D008969:Molecular Sequence Data; D010012:Osteogenesis / Q000235:genetics*; D011494:Protein Kinases / Q000235:genetics* / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D017422:Sequence Analysis, DNA; D050053:TRPM Cation Channels; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics
chemical_list: D018076:DNA, Complementary; D007473:Ion Channels; D050053:TRPM Cation Channels; D029961:Zebrafish Proteins; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; C501875:Trpm7 protein, zebrafish