Partial rescue of the ocular retardation phenotype by genetic modifiers

Cynthia Bone-Larson, Sharmila Basu, Jeffrey D. Radel, Meiying Liang, Timothy Perozek, Natalia Kapousta-Bruneau, Daniel G. Green, Margit Burmeister, Mark Hankin

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

The or(J) allele of the murine ocular retardation mutation is caused by a premature stop codon in the homeodomain of the Chx10 gene. When expressed on an inbred 129/Sv strain, the or(J) phenotype is characterized by microphthalmia and a thin, poorly differentiated retina in which the peripheral portion is affected to a greater extent than the central portion. Such mutant retinae lack differentiated bipolar cells and the optic nerve typically fails to form, leading to blindness. Here, we show that progeny from an outcrossed backcross between 129/Sv-or(J)/or(J) and Mus musculus castaneus produce animals that are homozygous for the or(J) mutation and exhibit a much ameliorated eye phenotype. Although not of normal size, such modified or(J) eyes are significantly larger than those in 129/Sv-or(J)/or(J) mice, and contain a better organized retina which includes bipolar cells. Furthermore, optic nerves are frequently present, and the eyes show a degree of function as reflected by electroretinogram and pupillary response. As in 129/Sv-or(J)/or(J) mice, however, modified or(J) eyes show incomplete growth and a lack of cell differentiation in the periphery of the retina. The selective, and apparently nonmodifiable, effect of the ocular retardation phenotype on the periphery of the retina indicates that Chx10 plays an important role in the central-to-peripheral gradient of retinal development. These findings demonstrate that the ocular retardation phenotype can be greatly modified by the genetic background, and help to define a role for Chx10 in ocular development.

Original languageEnglish (US)
Pages (from-to)232-247
Number of pages16
JournalJournal of Neurobiology
Volume42
Issue number2
DOIs
StatePublished - Jan 31 2000
Externally publishedYes

Fingerprint

Phenotype
Retina
Optic Nerve
Microphthalmos
Mutation
Nonsense Codon
Blindness
Cell Differentiation
Alleles
Growth
Genes

Keywords

  • Chx10 homeobox gene
  • Microphthalmia
  • Mouse
  • Optic nerve
  • Retina

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Partial rescue of the ocular retardation phenotype by genetic modifiers. / Bone-Larson, Cynthia; Basu, Sharmila; Radel, Jeffrey D.; Liang, Meiying; Perozek, Timothy; Kapousta-Bruneau, Natalia; Green, Daniel G.; Burmeister, Margit; Hankin, Mark.

In: Journal of Neurobiology, Vol. 42, No. 2, 31.01.2000, p. 232-247.

Research output: Contribution to journalArticle

Bone-Larson, C, Basu, S, Radel, JD, Liang, M, Perozek, T, Kapousta-Bruneau, N, Green, DG, Burmeister, M & Hankin, M 2000, 'Partial rescue of the ocular retardation phenotype by genetic modifiers', Journal of Neurobiology, vol. 42, no. 2, pp. 232-247. https://doi.org/10.1002/(SICI)1097-4695(20000205)42:2<232::AID-NEU7>3.0.CO;2-4
Bone-Larson, Cynthia ; Basu, Sharmila ; Radel, Jeffrey D. ; Liang, Meiying ; Perozek, Timothy ; Kapousta-Bruneau, Natalia ; Green, Daniel G. ; Burmeister, Margit ; Hankin, Mark. / Partial rescue of the ocular retardation phenotype by genetic modifiers. In: Journal of Neurobiology. 2000 ; Vol. 42, No. 2. pp. 232-247.
@article{046d8253ecad4a07ac08e03851578e13,
title = "Partial rescue of the ocular retardation phenotype by genetic modifiers",
abstract = "The or(J) allele of the murine ocular retardation mutation is caused by a premature stop codon in the homeodomain of the Chx10 gene. When expressed on an inbred 129/Sv strain, the or(J) phenotype is characterized by microphthalmia and a thin, poorly differentiated retina in which the peripheral portion is affected to a greater extent than the central portion. Such mutant retinae lack differentiated bipolar cells and the optic nerve typically fails to form, leading to blindness. Here, we show that progeny from an outcrossed backcross between 129/Sv-or(J)/or(J) and Mus musculus castaneus produce animals that are homozygous for the or(J) mutation and exhibit a much ameliorated eye phenotype. Although not of normal size, such modified or(J) eyes are significantly larger than those in 129/Sv-or(J)/or(J) mice, and contain a better organized retina which includes bipolar cells. Furthermore, optic nerves are frequently present, and the eyes show a degree of function as reflected by electroretinogram and pupillary response. As in 129/Sv-or(J)/or(J) mice, however, modified or(J) eyes show incomplete growth and a lack of cell differentiation in the periphery of the retina. The selective, and apparently nonmodifiable, effect of the ocular retardation phenotype on the periphery of the retina indicates that Chx10 plays an important role in the central-to-peripheral gradient of retinal development. These findings demonstrate that the ocular retardation phenotype can be greatly modified by the genetic background, and help to define a role for Chx10 in ocular development.",
keywords = "Chx10 homeobox gene, Microphthalmia, Mouse, Optic nerve, Retina",
author = "Cynthia Bone-Larson and Sharmila Basu and Radel, {Jeffrey D.} and Meiying Liang and Timothy Perozek and Natalia Kapousta-Bruneau and Green, {Daniel G.} and Margit Burmeister and Mark Hankin",
year = "2000",
month = "1",
day = "31",
doi = "10.1002/(SICI)1097-4695(20000205)42:2<232::AID-NEU7>3.0.CO;2-4",
language = "English (US)",
volume = "42",
pages = "232--247",
journal = "Developmental Neurobiology",
issn = "1932-8451",
publisher = "John Wiley and Sons Inc.",
number = "2",

}

TY - JOUR

T1 - Partial rescue of the ocular retardation phenotype by genetic modifiers

AU - Bone-Larson, Cynthia

AU - Basu, Sharmila

AU - Radel, Jeffrey D.

AU - Liang, Meiying

AU - Perozek, Timothy

AU - Kapousta-Bruneau, Natalia

AU - Green, Daniel G.

AU - Burmeister, Margit

AU - Hankin, Mark

PY - 2000/1/31

Y1 - 2000/1/31

N2 - The or(J) allele of the murine ocular retardation mutation is caused by a premature stop codon in the homeodomain of the Chx10 gene. When expressed on an inbred 129/Sv strain, the or(J) phenotype is characterized by microphthalmia and a thin, poorly differentiated retina in which the peripheral portion is affected to a greater extent than the central portion. Such mutant retinae lack differentiated bipolar cells and the optic nerve typically fails to form, leading to blindness. Here, we show that progeny from an outcrossed backcross between 129/Sv-or(J)/or(J) and Mus musculus castaneus produce animals that are homozygous for the or(J) mutation and exhibit a much ameliorated eye phenotype. Although not of normal size, such modified or(J) eyes are significantly larger than those in 129/Sv-or(J)/or(J) mice, and contain a better organized retina which includes bipolar cells. Furthermore, optic nerves are frequently present, and the eyes show a degree of function as reflected by electroretinogram and pupillary response. As in 129/Sv-or(J)/or(J) mice, however, modified or(J) eyes show incomplete growth and a lack of cell differentiation in the periphery of the retina. The selective, and apparently nonmodifiable, effect of the ocular retardation phenotype on the periphery of the retina indicates that Chx10 plays an important role in the central-to-peripheral gradient of retinal development. These findings demonstrate that the ocular retardation phenotype can be greatly modified by the genetic background, and help to define a role for Chx10 in ocular development.

AB - The or(J) allele of the murine ocular retardation mutation is caused by a premature stop codon in the homeodomain of the Chx10 gene. When expressed on an inbred 129/Sv strain, the or(J) phenotype is characterized by microphthalmia and a thin, poorly differentiated retina in which the peripheral portion is affected to a greater extent than the central portion. Such mutant retinae lack differentiated bipolar cells and the optic nerve typically fails to form, leading to blindness. Here, we show that progeny from an outcrossed backcross between 129/Sv-or(J)/or(J) and Mus musculus castaneus produce animals that are homozygous for the or(J) mutation and exhibit a much ameliorated eye phenotype. Although not of normal size, such modified or(J) eyes are significantly larger than those in 129/Sv-or(J)/or(J) mice, and contain a better organized retina which includes bipolar cells. Furthermore, optic nerves are frequently present, and the eyes show a degree of function as reflected by electroretinogram and pupillary response. As in 129/Sv-or(J)/or(J) mice, however, modified or(J) eyes show incomplete growth and a lack of cell differentiation in the periphery of the retina. The selective, and apparently nonmodifiable, effect of the ocular retardation phenotype on the periphery of the retina indicates that Chx10 plays an important role in the central-to-peripheral gradient of retinal development. These findings demonstrate that the ocular retardation phenotype can be greatly modified by the genetic background, and help to define a role for Chx10 in ocular development.

KW - Chx10 homeobox gene

KW - Microphthalmia

KW - Mouse

KW - Optic nerve

KW - Retina

UR - http://www.scopus.com/inward/record.url?scp=0033954738&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033954738&partnerID=8YFLogxK

U2 - 10.1002/(SICI)1097-4695(20000205)42:2<232::AID-NEU7>3.0.CO;2-4

DO - 10.1002/(SICI)1097-4695(20000205)42:2<232::AID-NEU7>3.0.CO;2-4

M3 - Article

C2 - 10640330

AN - SCOPUS:0033954738

VL - 42

SP - 232

EP - 247

JO - Developmental Neurobiology

JF - Developmental Neurobiology

SN - 1932-8451

IS - 2

ER -