Fine-mapping quantitative trait loci affecting murine external ear tissue regeneration in the LG/J by SM/J advanced intercross line

J. M. Cheverud; H. A. Lawson; K. Bouckaert; A. V. Kossenkov; L. C. Showe; L. Cort; E. P. Blankenhorn; K. Bedelbaeva; D. Gourevitch; Y. Zhang; E. Heber-Katz

doi:10.1038/hdy.2013.133

Fine-mapping quantitative trait loci affecting murine external ear tissue regeneration in the LG/J by SM/J advanced intercross line

J. M. Cheverud
, H. A. Lawson
, K. Bouckaert
, A. V. Kossenkov
, L. C. Showe
, L. Cort
, E. P. Blankenhorn
, K. Bedelbaeva
, D. Gourevitch
, Y. Zhang
, E. Heber-Katz

Research output: Contribution to journal › Article › peer-review

25 Scopus citations

Abstract

External ear hole closure in LG/J mice represents a model of regenerative response. It is accompanied by the formation of a blastema-like structure and the re-growth of multiple tissues, including cartilage the ability to regenerate tissue is heritable. An F34 advanced intercross line of mice (Wustl:LG,SM-G34) was generated to identify genomic loci involved in ear hole closure over a 30-day healing period. We mapped 19 quantitative trait loci (QTL) for ear hole closure. Individual gene effects are relatively small (0.08 mm), and most loci have co-dominant effects with phenotypically intermediate heterozygotes. QTL support regions were limited to a median size of 2 Mb containing a median of 19 genes. Positional candidate genes were evaluated using differential transcript expression between LG/J and SM/J healing tissue, function analysis and bioinformatic analysis of single-nucleotide polymorphisms in and around positional candidate genes of interest. Analysis of the set of 34 positional candidate genes and those displaying expression differences revealed over-representation of genes involved in cell cycle regulation/DNA damage, cell migration and adhesion, developmentally related genes and metabolism. This indicates that the healing phenotype in LG/J mice involves multiple physiological mechanisms.

Original language	English
Pages (from-to)	508-518
Number of pages	11
Journal	Heredity
Volume	112
Issue number	5
DOIs	https://doi.org/10.1038/hdy.2013.133
State	Published - May 2014

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Cheverud, J. M., Lawson, H. A., Bouckaert, K., Kossenkov, A. V., Showe, L. C., Cort, L., Blankenhorn, E. P., Bedelbaeva, K., Gourevitch, D., Zhang, Y., & Heber-Katz, E. (2014). Fine-mapping quantitative trait loci affecting murine external ear tissue regeneration in the LG/J by SM/J advanced intercross line. Heredity, 112(5), 508-518. https://doi.org/10.1038/hdy.2013.133

@article{a61b6dcd868b4b81bc3e4c03d6532698,

title = "Fine-mapping quantitative trait loci affecting murine external ear tissue regeneration in the LG/J by SM/J advanced intercross line",

abstract = "External ear hole closure in LG/J mice represents a model of regenerative response. It is accompanied by the formation of a blastema-like structure and the re-growth of multiple tissues, including cartilage the ability to regenerate tissue is heritable. An F34 advanced intercross line of mice (Wustl:LG,SM-G34) was generated to identify genomic loci involved in ear hole closure over a 30-day healing period. We mapped 19 quantitative trait loci (QTL) for ear hole closure. Individual gene effects are relatively small (0.08 mm), and most loci have co-dominant effects with phenotypically intermediate heterozygotes. QTL support regions were limited to a median size of 2 Mb containing a median of 19 genes. Positional candidate genes were evaluated using differential transcript expression between LG/J and SM/J healing tissue, function analysis and bioinformatic analysis of single-nucleotide polymorphisms in and around positional candidate genes of interest. Analysis of the set of 34 positional candidate genes and those displaying expression differences revealed over-representation of genes involved in cell cycle regulation/DNA damage, cell migration and adhesion, developmentally related genes and metabolism. This indicates that the healing phenotype in LG/J mice involves multiple physiological mechanisms.",

author = "Cheverud, \{J. M.\} and Lawson, \{H. A.\} and K. Bouckaert and Kossenkov, \{A. V.\} and Showe, \{L. C.\} and L. Cort and Blankenhorn, \{E. P.\} and K. Bedelbaeva and D. Gourevitch and Y. Zhang and E. Heber-Katz",

note = "Funding Information: A second gene, Wnt3a (Q11.1), is involved in proliferation and regenerative healing and is also upregulated (expression ratio = + 1.96) in LG/J. We examined WNT3a protein expression in LG/J and SM/J ear tissue throughout a 21-day post-injury period of healing by immunostaining (Figures 2a and b) and found a significant difference in level and location of expression. In the epidermis, WNT3a is high in LG/J from day 7 through day 21 of healing but only sparsely present on day 7 in SM/J; in the dermis, WNT3a is high in LG/J ear on days 7 and 14 (Figure 2a). This is supported by western blotting analysis (Figure 2f).",

year = "2014",

month = may,

doi = "10.1038/hdy.2013.133",

language = "English",

volume = "112",

pages = "508--518",

journal = "Heredity",

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T1 - Fine-mapping quantitative trait loci affecting murine external ear tissue regeneration in the LG/J by SM/J advanced intercross line

AU - Cheverud, J. M.

AU - Lawson, H. A.

AU - Bouckaert, K.

AU - Kossenkov, A. V.

AU - Showe, L. C.

AU - Cort, L.

AU - Blankenhorn, E. P.

AU - Bedelbaeva, K.

AU - Gourevitch, D.

AU - Zhang, Y.

AU - Heber-Katz, E.

N1 - Funding Information: A second gene, Wnt3a (Q11.1), is involved in proliferation and regenerative healing and is also upregulated (expression ratio = + 1.96) in LG/J. We examined WNT3a protein expression in LG/J and SM/J ear tissue throughout a 21-day post-injury period of healing by immunostaining (Figures 2a and b) and found a significant difference in level and location of expression. In the epidermis, WNT3a is high in LG/J from day 7 through day 21 of healing but only sparsely present on day 7 in SM/J; in the dermis, WNT3a is high in LG/J ear on days 7 and 14 (Figure 2a). This is supported by western blotting analysis (Figure 2f).

PY - 2014/5

Y1 - 2014/5

N2 - External ear hole closure in LG/J mice represents a model of regenerative response. It is accompanied by the formation of a blastema-like structure and the re-growth of multiple tissues, including cartilage the ability to regenerate tissue is heritable. An F34 advanced intercross line of mice (Wustl:LG,SM-G34) was generated to identify genomic loci involved in ear hole closure over a 30-day healing period. We mapped 19 quantitative trait loci (QTL) for ear hole closure. Individual gene effects are relatively small (0.08 mm), and most loci have co-dominant effects with phenotypically intermediate heterozygotes. QTL support regions were limited to a median size of 2 Mb containing a median of 19 genes. Positional candidate genes were evaluated using differential transcript expression between LG/J and SM/J healing tissue, function analysis and bioinformatic analysis of single-nucleotide polymorphisms in and around positional candidate genes of interest. Analysis of the set of 34 positional candidate genes and those displaying expression differences revealed over-representation of genes involved in cell cycle regulation/DNA damage, cell migration and adhesion, developmentally related genes and metabolism. This indicates that the healing phenotype in LG/J mice involves multiple physiological mechanisms.

AB - External ear hole closure in LG/J mice represents a model of regenerative response. It is accompanied by the formation of a blastema-like structure and the re-growth of multiple tissues, including cartilage the ability to regenerate tissue is heritable. An F34 advanced intercross line of mice (Wustl:LG,SM-G34) was generated to identify genomic loci involved in ear hole closure over a 30-day healing period. We mapped 19 quantitative trait loci (QTL) for ear hole closure. Individual gene effects are relatively small (0.08 mm), and most loci have co-dominant effects with phenotypically intermediate heterozygotes. QTL support regions were limited to a median size of 2 Mb containing a median of 19 genes. Positional candidate genes were evaluated using differential transcript expression between LG/J and SM/J healing tissue, function analysis and bioinformatic analysis of single-nucleotide polymorphisms in and around positional candidate genes of interest. Analysis of the set of 34 positional candidate genes and those displaying expression differences revealed over-representation of genes involved in cell cycle regulation/DNA damage, cell migration and adhesion, developmentally related genes and metabolism. This indicates that the healing phenotype in LG/J mice involves multiple physiological mechanisms.

UR - https://www.scopus.com/pages/publications/84899464011

U2 - 10.1038/hdy.2013.133

DO - 10.1038/hdy.2013.133

M3 - Article

C2 - 24569637

AN - SCOPUS:84899464011

SN - 0018-067X

VL - 112

SP - 508

EP - 518

JO - Heredity

JF - Heredity

IS - 5

ER -

Fine-mapping quantitative trait loci affecting murine external ear tissue regeneration in the LG/J by SM/J advanced intercross line

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