Mutations in the Katnb1 gene cause left-right asymmetry and heart defects

Research output: Contribution to journalArticleResearchpeer-review

Abstract

The microtubule-severing protein complex katanin is composed two subunits, the ATPase subunit, KATNA1, and the non-catalytic regulatory subunit, KATNB1. Recently, the Katnb1 gene has been linked to infertility, regulation of centriole and cilia formation in fish and mammals, as well as neocortical brain development. KATNB1 protein is expressed in germ cells in humans and mouse, mitotic/meiotic spindles and cilia, although the full expression pattern of the Katnb1 gene has not been described. Results: Using a knockin-knockout mouse model of Katnb1 dysfunction we demonstrate that Katnb1 is ubiquitously expressed during embryonic development, although a stronger expression is seen in the crown cells of the gastrulation organizer, the murine node. Furthermore, null and hypomorphic Katnb1 gene mutations show a novel correlation between Katnb1 dysregulation and the development of impaired left-right signaling, including cardiac malformations. Conclusion: Katanin function is a critical regulator of heart development in mice. These findings are potentially relevant to human cardiac development.
Original languageEnglish
Pages (from-to)1027-1035
Number of pages9
JournalDevelopmental Dynamics
Volume246
Issue number12
DOIs
Publication statusPublished - Dec 2017

Keywords

  • cilia
  • Katnb1
  • heart
  • development
  • katanin
  • microtubules

Cite this

@article{fa4d25bfbcf64a6596c4c6a7c853e5ac,
title = "Mutations in the Katnb1 gene cause left-right asymmetry and heart defects",
abstract = "The microtubule-severing protein complex katanin is composed two subunits, the ATPase subunit, KATNA1, and the non-catalytic regulatory subunit, KATNB1. Recently, the Katnb1 gene has been linked to infertility, regulation of centriole and cilia formation in fish and mammals, as well as neocortical brain development. KATNB1 protein is expressed in germ cells in humans and mouse, mitotic/meiotic spindles and cilia, although the full expression pattern of the Katnb1 gene has not been described. Results: Using a knockin-knockout mouse model of Katnb1 dysfunction we demonstrate that Katnb1 is ubiquitously expressed during embryonic development, although a stronger expression is seen in the crown cells of the gastrulation organizer, the murine node. Furthermore, null and hypomorphic Katnb1 gene mutations show a novel correlation between Katnb1 dysregulation and the development of impaired left-right signaling, including cardiac malformations. Conclusion: Katanin function is a critical regulator of heart development in mice. These findings are potentially relevant to human cardiac development.",
keywords = "cilia, Katnb1, heart, development, katanin, microtubules",
author = "M.B. Furtado and D.J. Merriner and S. Berger and D. Rhodes and D. Jamsai and M.K. O'Bryan",
year = "2017",
month = "12",
doi = "10.1002/dvdy.24564",
language = "English",
volume = "246",
pages = "1027--1035",
journal = "Developmental Dynamics",
issn = "1058-8388",
publisher = "Wiley-Blackwell",
number = "12",

}

Mutations in the Katnb1 gene cause left-right asymmetry and heart defects. / Furtado, M.B.; Merriner, D.J.; Berger, S.; Rhodes, D.; Jamsai, D.; O'Bryan, M.K.

In: Developmental Dynamics, Vol. 246, No. 12, 12.2017, p. 1027-1035.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Mutations in the Katnb1 gene cause left-right asymmetry and heart defects

AU - Furtado, M.B.

AU - Merriner, D.J.

AU - Berger, S.

AU - Rhodes, D.

AU - Jamsai, D.

AU - O'Bryan, M.K.

PY - 2017/12

Y1 - 2017/12

N2 - The microtubule-severing protein complex katanin is composed two subunits, the ATPase subunit, KATNA1, and the non-catalytic regulatory subunit, KATNB1. Recently, the Katnb1 gene has been linked to infertility, regulation of centriole and cilia formation in fish and mammals, as well as neocortical brain development. KATNB1 protein is expressed in germ cells in humans and mouse, mitotic/meiotic spindles and cilia, although the full expression pattern of the Katnb1 gene has not been described. Results: Using a knockin-knockout mouse model of Katnb1 dysfunction we demonstrate that Katnb1 is ubiquitously expressed during embryonic development, although a stronger expression is seen in the crown cells of the gastrulation organizer, the murine node. Furthermore, null and hypomorphic Katnb1 gene mutations show a novel correlation between Katnb1 dysregulation and the development of impaired left-right signaling, including cardiac malformations. Conclusion: Katanin function is a critical regulator of heart development in mice. These findings are potentially relevant to human cardiac development.

AB - The microtubule-severing protein complex katanin is composed two subunits, the ATPase subunit, KATNA1, and the non-catalytic regulatory subunit, KATNB1. Recently, the Katnb1 gene has been linked to infertility, regulation of centriole and cilia formation in fish and mammals, as well as neocortical brain development. KATNB1 protein is expressed in germ cells in humans and mouse, mitotic/meiotic spindles and cilia, although the full expression pattern of the Katnb1 gene has not been described. Results: Using a knockin-knockout mouse model of Katnb1 dysfunction we demonstrate that Katnb1 is ubiquitously expressed during embryonic development, although a stronger expression is seen in the crown cells of the gastrulation organizer, the murine node. Furthermore, null and hypomorphic Katnb1 gene mutations show a novel correlation between Katnb1 dysregulation and the development of impaired left-right signaling, including cardiac malformations. Conclusion: Katanin function is a critical regulator of heart development in mice. These findings are potentially relevant to human cardiac development.

KW - cilia

KW - Katnb1

KW - heart

KW - development

KW - katanin

KW - microtubules

UR - http://www.scopus.com/inward/record.url?scp=85028872535&partnerID=8YFLogxK

U2 - 10.1002/dvdy.24564

DO - 10.1002/dvdy.24564

M3 - Article

VL - 246

SP - 1027

EP - 1035

JO - Developmental Dynamics

JF - Developmental Dynamics

SN - 1058-8388

IS - 12

ER -