Hypopigmentation and Maternal-Zygotic Embryonic Lethality Caused by a Hypomorphic Mbtps1 Mutation in Mice

Sophie Rutschmann, Karine Crozat, Xiaohong Li, Xin Du, Jeffrey C. Hanselman, Alana A. Shigeoka, Katharina Brandl, Daniel L. Popkin, Dianne B. McKay, Yu Xia, Eva Marie Y Moresco, Bruce Beutler

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

The site 1 protease, encoded by Mbtps1, mediates the initial cleavage of site 2 protease substrates, including sterol regulatory element binding proteins and CREB/ATF transcription factors. We demonstrate that a hypomorphic mutation of Mbtps1 called woodrat (wrt) caused hypocholesterolemia, as well as progressive hypopigmentation of the coat, that appears to be mechanistically unrelated. Hypopigmentation was rescued by transgenic expression of wild-type Mbtps1, and reciprocal grafting studies showed that normal pigmentation depended upon both cell-intrinsic or paracrine factors, as well as factors that act systemically, both of which are lacking in wrt homozygotes. Mbtps1 exhibited a maternal-zygotic effect characterized by fully penetrant embryonic lethality of maternal-zygotic wrt mutant offspring and partial embryonic lethality (~40%) of zygotic wrt mutant offspring. Mbtps1 is one of two maternal-zygotic effect genes identified in mammals to date. It functions nonredundantly in pigmentation and embryogenesis.

Original languageEnglish (US)
Pages (from-to)499-504
Number of pages6
JournalG3: Genes, Genomes, Genetics
Volume2
Issue number4
DOIs
StatePublished - Apr 2012

Fingerprint

Hypopigmentation
Pigmentation
Sterol Regulatory Element Binding Proteins
Activating Transcription Factors
Mothers
Mutation
Homozygote
Embryonic Development
Mammals
Peptide Hydrolases
Genes
Maternal Inheritance
site 1 membrane-bound transcription factor peptidase

Keywords

  • Cholesterol
  • Coat color
  • Effect lethality
  • Maternal-zygotic
  • Pigmentation
  • Site 1 protease

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Genetics(clinical)

Cite this

Hypopigmentation and Maternal-Zygotic Embryonic Lethality Caused by a Hypomorphic Mbtps1 Mutation in Mice. / Rutschmann, Sophie; Crozat, Karine; Li, Xiaohong; Du, Xin; Hanselman, Jeffrey C.; Shigeoka, Alana A.; Brandl, Katharina; Popkin, Daniel L.; McKay, Dianne B.; Xia, Yu; Moresco, Eva Marie Y; Beutler, Bruce.

In: G3: Genes, Genomes, Genetics, Vol. 2, No. 4, 04.2012, p. 499-504.

Research output: Contribution to journalArticle

Rutschmann, S, Crozat, K, Li, X, Du, X, Hanselman, JC, Shigeoka, AA, Brandl, K, Popkin, DL, McKay, DB, Xia, Y, Moresco, EMY & Beutler, B 2012, 'Hypopigmentation and Maternal-Zygotic Embryonic Lethality Caused by a Hypomorphic Mbtps1 Mutation in Mice', G3: Genes, Genomes, Genetics, vol. 2, no. 4, pp. 499-504. https://doi.org/10.1534/g3.112.002196
Rutschmann, Sophie ; Crozat, Karine ; Li, Xiaohong ; Du, Xin ; Hanselman, Jeffrey C. ; Shigeoka, Alana A. ; Brandl, Katharina ; Popkin, Daniel L. ; McKay, Dianne B. ; Xia, Yu ; Moresco, Eva Marie Y ; Beutler, Bruce. / Hypopigmentation and Maternal-Zygotic Embryonic Lethality Caused by a Hypomorphic Mbtps1 Mutation in Mice. In: G3: Genes, Genomes, Genetics. 2012 ; Vol. 2, No. 4. pp. 499-504.
@article{d4047090a35b4d0290691d2bcab04d8c,
title = "Hypopigmentation and Maternal-Zygotic Embryonic Lethality Caused by a Hypomorphic Mbtps1 Mutation in Mice",
abstract = "The site 1 protease, encoded by Mbtps1, mediates the initial cleavage of site 2 protease substrates, including sterol regulatory element binding proteins and CREB/ATF transcription factors. We demonstrate that a hypomorphic mutation of Mbtps1 called woodrat (wrt) caused hypocholesterolemia, as well as progressive hypopigmentation of the coat, that appears to be mechanistically unrelated. Hypopigmentation was rescued by transgenic expression of wild-type Mbtps1, and reciprocal grafting studies showed that normal pigmentation depended upon both cell-intrinsic or paracrine factors, as well as factors that act systemically, both of which are lacking in wrt homozygotes. Mbtps1 exhibited a maternal-zygotic effect characterized by fully penetrant embryonic lethality of maternal-zygotic wrt mutant offspring and partial embryonic lethality (~40{\%}) of zygotic wrt mutant offspring. Mbtps1 is one of two maternal-zygotic effect genes identified in mammals to date. It functions nonredundantly in pigmentation and embryogenesis.",
keywords = "Cholesterol, Coat color, Effect lethality, Maternal-zygotic, Pigmentation, Site 1 protease",
author = "Sophie Rutschmann and Karine Crozat and Xiaohong Li and Xin Du and Hanselman, {Jeffrey C.} and Shigeoka, {Alana A.} and Katharina Brandl and Popkin, {Daniel L.} and McKay, {Dianne B.} and Yu Xia and Moresco, {Eva Marie Y} and Bruce Beutler",
year = "2012",
month = "4",
doi = "10.1534/g3.112.002196",
language = "English (US)",
volume = "2",
pages = "499--504",
journal = "G3 (Bethesda, Md.)",
issn = "2160-1836",
publisher = "Genetics Society of America",
number = "4",

}

TY - JOUR

T1 - Hypopigmentation and Maternal-Zygotic Embryonic Lethality Caused by a Hypomorphic Mbtps1 Mutation in Mice

AU - Rutschmann, Sophie

AU - Crozat, Karine

AU - Li, Xiaohong

AU - Du, Xin

AU - Hanselman, Jeffrey C.

AU - Shigeoka, Alana A.

AU - Brandl, Katharina

AU - Popkin, Daniel L.

AU - McKay, Dianne B.

AU - Xia, Yu

AU - Moresco, Eva Marie Y

AU - Beutler, Bruce

PY - 2012/4

Y1 - 2012/4

N2 - The site 1 protease, encoded by Mbtps1, mediates the initial cleavage of site 2 protease substrates, including sterol regulatory element binding proteins and CREB/ATF transcription factors. We demonstrate that a hypomorphic mutation of Mbtps1 called woodrat (wrt) caused hypocholesterolemia, as well as progressive hypopigmentation of the coat, that appears to be mechanistically unrelated. Hypopigmentation was rescued by transgenic expression of wild-type Mbtps1, and reciprocal grafting studies showed that normal pigmentation depended upon both cell-intrinsic or paracrine factors, as well as factors that act systemically, both of which are lacking in wrt homozygotes. Mbtps1 exhibited a maternal-zygotic effect characterized by fully penetrant embryonic lethality of maternal-zygotic wrt mutant offspring and partial embryonic lethality (~40%) of zygotic wrt mutant offspring. Mbtps1 is one of two maternal-zygotic effect genes identified in mammals to date. It functions nonredundantly in pigmentation and embryogenesis.

AB - The site 1 protease, encoded by Mbtps1, mediates the initial cleavage of site 2 protease substrates, including sterol regulatory element binding proteins and CREB/ATF transcription factors. We demonstrate that a hypomorphic mutation of Mbtps1 called woodrat (wrt) caused hypocholesterolemia, as well as progressive hypopigmentation of the coat, that appears to be mechanistically unrelated. Hypopigmentation was rescued by transgenic expression of wild-type Mbtps1, and reciprocal grafting studies showed that normal pigmentation depended upon both cell-intrinsic or paracrine factors, as well as factors that act systemically, both of which are lacking in wrt homozygotes. Mbtps1 exhibited a maternal-zygotic effect characterized by fully penetrant embryonic lethality of maternal-zygotic wrt mutant offspring and partial embryonic lethality (~40%) of zygotic wrt mutant offspring. Mbtps1 is one of two maternal-zygotic effect genes identified in mammals to date. It functions nonredundantly in pigmentation and embryogenesis.

KW - Cholesterol

KW - Coat color

KW - Effect lethality

KW - Maternal-zygotic

KW - Pigmentation

KW - Site 1 protease

UR - http://www.scopus.com/inward/record.url?scp=84868156281&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84868156281&partnerID=8YFLogxK

U2 - 10.1534/g3.112.002196

DO - 10.1534/g3.112.002196

M3 - Article

C2 - 22540041

AN - SCOPUS:84868156281

VL - 2

SP - 499

EP - 504

JO - G3 (Bethesda, Md.)

JF - G3 (Bethesda, Md.)

SN - 2160-1836

IS - 4

ER -