Penetrance of eye defects in mice heterozygous for mutation of Gli3 is enhanced by heterozygous mutation of Pax6

Paulette A. Zaki, J. Martin Collinson, Junko Toraiwa, T.Ian Simpson, David J. Price, J.C. Quinn

Research output: Contribution to journalArticle

13 Citations (Scopus)
1 Downloads (Pure)

Abstract

Background: Knowledge of the consequences of heterozygous mutations of developmentally important genes is important for understanding human genetic disorders. The Gli3 gene encodes a zinc finger transcription factor and homozygous loss-of-function mutations of Gli3 are lethal. Humans heterozygous for mutations in this gene suffer Greig cephalopolysyndactyly or Pallister-Hall syndromes, in which limb defects are prominent, and mice heterozygous for similar mutations have extra digits. Here we examined whether eye development, which is abnormal in mice lacking functional Gli3, is defective in Gli3 +/- mice. Results: We showed that Gli3 is expressed in the developing eye but that Gli3+/- mice have only very subtle eye defects. We then generated mice compound heterozygous for mutations in both Gli3 and Pax6, which encodes another developmentally important transcription factor known to be crucial for eye development. Pax6+/-; Gli3+/- eyes were compared to the eyes of wild-type, Pax6+/- or Gli3+/- siblings. They exhibited a range of abnormalities of the retina, iris, lens and cornea that was more extensive than in single Gli3+/- or Pax6 +/- mutants or than would be predicted by addition of their phenotypes. Conclusion: These findings indicate that heterozygous mutations of Gli3 can impact on eye development. The importance of a normal Gli3 gene dosage becomes greater in the absence of a normal Pax6 gene dosage, suggesting that the two genes co-operate during eye morphogenesis.
Original languageEnglish
Pages (from-to)1-11
Number of pages11
JournalBMC Developmental Biology
Volume6
Issue number46
DOIs
Publication statusPublished - 2006

Fingerprint

Penetrance
Mutation
Gene Dosage
Genes
Pallister-Hall Syndrome
Transcription Factors
Inborn Genetic Diseases
Zinc Fingers
Medical Genetics
Iris
Morphogenesis
Cornea
Lenses
Retina
Extremities
Phenotype

Cite this

Zaki, Paulette A. ; Collinson, J. Martin ; Toraiwa, Junko ; Simpson, T.Ian ; Price, David J. ; Quinn, J.C. / Penetrance of eye defects in mice heterozygous for mutation of Gli3 is enhanced by heterozygous mutation of Pax6. In: BMC Developmental Biology. 2006 ; Vol. 6, No. 46. pp. 1-11.
@article{21b09475404540a08b4f33035e00d80a,
title = "Penetrance of eye defects in mice heterozygous for mutation of Gli3 is enhanced by heterozygous mutation of Pax6",
abstract = "Background: Knowledge of the consequences of heterozygous mutations of developmentally important genes is important for understanding human genetic disorders. The Gli3 gene encodes a zinc finger transcription factor and homozygous loss-of-function mutations of Gli3 are lethal. Humans heterozygous for mutations in this gene suffer Greig cephalopolysyndactyly or Pallister-Hall syndromes, in which limb defects are prominent, and mice heterozygous for similar mutations have extra digits. Here we examined whether eye development, which is abnormal in mice lacking functional Gli3, is defective in Gli3 +/- mice. Results: We showed that Gli3 is expressed in the developing eye but that Gli3+/- mice have only very subtle eye defects. We then generated mice compound heterozygous for mutations in both Gli3 and Pax6, which encodes another developmentally important transcription factor known to be crucial for eye development. Pax6+/-; Gli3+/- eyes were compared to the eyes of wild-type, Pax6+/- or Gli3+/- siblings. They exhibited a range of abnormalities of the retina, iris, lens and cornea that was more extensive than in single Gli3+/- or Pax6 +/- mutants or than would be predicted by addition of their phenotypes. Conclusion: These findings indicate that heterozygous mutations of Gli3 can impact on eye development. The importance of a normal Gli3 gene dosage becomes greater in the absence of a normal Pax6 gene dosage, suggesting that the two genes co-operate during eye morphogenesis.",
keywords = "Open access version available",
author = "Zaki, {Paulette A.} and Collinson, {J. Martin} and Junko Toraiwa and T.Ian Simpson and Price, {David J.} and J.C. Quinn",
note = "Imported on 12 Apr 2017 - DigiTool details were: Journal title (773t) = BMC Developmental Biology. ISSNs: 1471-213X;",
year = "2006",
doi = "10.1186/1471-213X-6-46",
language = "English",
volume = "6",
pages = "1--11",
journal = "BMC Developmental Biology",
issn = "1471-213X",
publisher = "BioMed Central",
number = "46",

}

Penetrance of eye defects in mice heterozygous for mutation of Gli3 is enhanced by heterozygous mutation of Pax6. / Zaki, Paulette A.; Collinson, J. Martin; Toraiwa, Junko; Simpson, T.Ian; Price, David J.; Quinn, J.C.

In: BMC Developmental Biology, Vol. 6, No. 46, 2006, p. 1-11.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Penetrance of eye defects in mice heterozygous for mutation of Gli3 is enhanced by heterozygous mutation of Pax6

AU - Zaki, Paulette A.

AU - Collinson, J. Martin

AU - Toraiwa, Junko

AU - Simpson, T.Ian

AU - Price, David J.

AU - Quinn, J.C.

N1 - Imported on 12 Apr 2017 - DigiTool details were: Journal title (773t) = BMC Developmental Biology. ISSNs: 1471-213X;

PY - 2006

Y1 - 2006

N2 - Background: Knowledge of the consequences of heterozygous mutations of developmentally important genes is important for understanding human genetic disorders. The Gli3 gene encodes a zinc finger transcription factor and homozygous loss-of-function mutations of Gli3 are lethal. Humans heterozygous for mutations in this gene suffer Greig cephalopolysyndactyly or Pallister-Hall syndromes, in which limb defects are prominent, and mice heterozygous for similar mutations have extra digits. Here we examined whether eye development, which is abnormal in mice lacking functional Gli3, is defective in Gli3 +/- mice. Results: We showed that Gli3 is expressed in the developing eye but that Gli3+/- mice have only very subtle eye defects. We then generated mice compound heterozygous for mutations in both Gli3 and Pax6, which encodes another developmentally important transcription factor known to be crucial for eye development. Pax6+/-; Gli3+/- eyes were compared to the eyes of wild-type, Pax6+/- or Gli3+/- siblings. They exhibited a range of abnormalities of the retina, iris, lens and cornea that was more extensive than in single Gli3+/- or Pax6 +/- mutants or than would be predicted by addition of their phenotypes. Conclusion: These findings indicate that heterozygous mutations of Gli3 can impact on eye development. The importance of a normal Gli3 gene dosage becomes greater in the absence of a normal Pax6 gene dosage, suggesting that the two genes co-operate during eye morphogenesis.

AB - Background: Knowledge of the consequences of heterozygous mutations of developmentally important genes is important for understanding human genetic disorders. The Gli3 gene encodes a zinc finger transcription factor and homozygous loss-of-function mutations of Gli3 are lethal. Humans heterozygous for mutations in this gene suffer Greig cephalopolysyndactyly or Pallister-Hall syndromes, in which limb defects are prominent, and mice heterozygous for similar mutations have extra digits. Here we examined whether eye development, which is abnormal in mice lacking functional Gli3, is defective in Gli3 +/- mice. Results: We showed that Gli3 is expressed in the developing eye but that Gli3+/- mice have only very subtle eye defects. We then generated mice compound heterozygous for mutations in both Gli3 and Pax6, which encodes another developmentally important transcription factor known to be crucial for eye development. Pax6+/-; Gli3+/- eyes were compared to the eyes of wild-type, Pax6+/- or Gli3+/- siblings. They exhibited a range of abnormalities of the retina, iris, lens and cornea that was more extensive than in single Gli3+/- or Pax6 +/- mutants or than would be predicted by addition of their phenotypes. Conclusion: These findings indicate that heterozygous mutations of Gli3 can impact on eye development. The importance of a normal Gli3 gene dosage becomes greater in the absence of a normal Pax6 gene dosage, suggesting that the two genes co-operate during eye morphogenesis.

KW - Open access version available

U2 - 10.1186/1471-213X-6-46

DO - 10.1186/1471-213X-6-46

M3 - Article

VL - 6

SP - 1

EP - 11

JO - BMC Developmental Biology

JF - BMC Developmental Biology

SN - 1471-213X

IS - 46

ER -