Publications by authors named "Caleb S Heffner"

3 Publications

  • Page 1 of 1

A novel allele of Alx4 results in reduced Fgf10 expression and failure of eyelid fusion in mice.

Mamm Genome 2015 Apr 12;26(3-4):173-80. Epub 2015 Feb 12.

The Jackson Laboratory, 600 Main St., Bar Harbor, ME, 04609, USA.

Normal fusion of developing eyelids requires coordination of inductive signals from the eyelid mesenchyme with migration of the periderm cell layer and constriction of the eyelids across the eye. Failure of this process results in an eyelids open at birth (EOB) phenotype in mice. We have identified a novel spontaneous allele of Alx4 that displays EOB, in addition to polydactyly and cranial malformations. Alx4 is expressed in the eyelid mesenchyme prior to and during eyelid fusion in a domain overlapping the expression of genes that also play a role in normal eyelid development. We show that Alx4 mutant mice have reduced expression of Fgf10, a key factor expressed in the mesenchyme that is required for initiation of eyelid fusion by the periderm. This is accompanied by a reduced number of periderm cells expressing phosphorylated c-Jun, consistent with the incomplete ablation of Fgf10 expression. Together, these data demonstrate that eyelid fusion in mice requires the expression of Alx4, accompanied by the loss of normal expression of essential components of the eyelid fusion pathway.
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http://dx.doi.org/10.1007/s00335-015-9557-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4482110PMC
April 2015

Supporting conditional mouse mutagenesis with a comprehensive cre characterization resource.

Nat Commun 2012 ;3:1218

The Jackson Laboratory, 600 Main Street, Bar Harbor, Maine 04609, USA.

Full realization of the value of the loxP-flanked alleles generated by the International Knockout Mouse Consortium will require a large set of well-characterized cre-driver lines. However, many cre driver lines display excision activity beyond the intended tissue or cell type, and these data are frequently unavailable to the potential user. Here we describe a high-throughput pipeline to extend characterization of cre driver lines to document excision activity in a wide range of tissues at multiple time points and disseminate these data to the scientific community. Our results show that the majority of cre strains exhibit some degree of unreported recombinase activity. In addition, we observe frequent mosaicism, inconsistent activity and parent-of-origin effects. Together, these results highlight the importance of deep characterization of cre strains, and provide the scientific community with a critical resource for cre strain information.
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http://dx.doi.org/10.1038/ncomms2186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3514490PMC
March 2013

Mouse gestation length is genetically determined.

PLoS One 2010 Aug 25;5(8):e12418. Epub 2010 Aug 25.

The Jackson Laboratory, Bar Harbor, Maine, United States of America.

Background: Preterm birth is an enormous public health problem, affecting over 12% of live births and costing over $26 billion in the United States alone. The causes are complex, but twin studies support the role of genetics in determining gestation length. Despite widespread use of the mouse in studies of the genetics of preterm birth, there have been few studies that actually address the precise natural gestation length of the mouse, and to what degree the timing of labor and birth is genetically determined.

Methodology/principal Findings: To further develop the mouse as a genetic model of preterm birth, we developed a high-throughput monitoring system and measured the gestation length in 15 inbred strains. Our results show an unexpectedly wide variation in overall gestation length between strains that approaches two full days, while intra-strain variation is quite low. Although litter size shows a strong inverse correlation with gestation length, genetic difference alone accounts for a significant portion of the variation. In addition, ovarian transplant experiments support a primary role of maternal genetics in the determination of gestation length. Preliminary analysis of gestation length in the C57BL/6J-Chr#(A/J)/NaJ chromosome substitution strain (B.A CSS) panel suggests complex genetic control of gestation length.

Conclusions/significance: Together, these data support the role of genetics in regulating gestation length and present the mouse as an important tool for the discovery of genes governing preterm birth.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0012418PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2928290PMC
August 2010