Phenotype Image Detail

Image

Caption

Lhx2 is required for anagen progression. (A) A Lhx2^tm1.1Lcar/Lhx2^tm1Dra (Lhx2^flox/-) control mouse (upper panel) and a Lhx2^tm1.1Lcar/Lhx2^tm1Dra Tg(CAG-cre/Esr1*)5Amc/0 (CreER:Lhx2^flox/-) mouse (lower panel) that were shaved and treated with tamoxifen (Tx) during the first postnatal telogen and analysed during late first postnatal anagen. Hair has re-grown on the shaved area in the control mouse but not in the mutant mouse. (B,C) H/E staining of sections of skin from Tx-treated control mice in early anagen (B, Sub-stage III) and late anagen (C, Sub-stage VI). (D-F) H/E staining of sections of skin from Tx-treated mutant mice within the Tx-treated area (D,E) and outside of the Tx-treated area (F). Mutant hair follicles (HFs) initiated anagen and developed to Sub-stage III similar to control mice (D, early anagen), but these HFs were arrested at this stage and were unable to assemble a normal hair shaft (E, late anagen). Hair shafts developed in HFs outside of the Tx-treated area in the mutant mice (F). (G) In situ hybridization analyses of Lhx2 expression in HFs in anagen in Tx-treated control animals (upper panels) and mutant animals (lower panels) using a full length (fl) Lhx2 cDNA probe (left panels) or a probe restricted to exon 2 (right panels). Control HFs revealed hybridization to both probes whereas the mutated HFs only hybridized to the full length probe confirming the expression of the truncated Lhx2 mRNA in the HFs where Lhx2 has been conditionally inactivated. (H) Immunohistochemical analysis of Lhx2 expression using an anti-Lhx2 antibody in control HFs (upper panel) and in HFs where Lhx2 has been conditionally inactivated (lower panel). (I) In situ hybridization analysis of expression of the S-phase-specific gene His1h3c in control anagen HFs (upper panel) and in anagen HFs where Lhx2 has been conditionally inactivated (lower panel). (J) Comparison of gene expression using in situ hybridization of the indicated genes between control anagen HFs (upper panel) and anagen HFs where Lhx2 has been conditionally inactivated (lower panel). Comparison of accumulation of the activated form of b-catenin (brown staining) in control HFs (upper right panel) and in HFs where Lhx2 has been inactivated (lower right panel) using an antibody specific for the dephosphorylated form of beta-catenin. (K) Morphological and gene expression analyses of a Tx-treated mutant mouse that has not re-grown the hair at 9 weeks of age. H/E staining of sections of skin revealing that normal hair shafts are not assembled (left panel, compared to control skin in C). Cells in the mutant HFs express Lhx2 mRNA that hybridize to the full length Lhx2 probe (fl. arrows) but not the exon-2 specific probe revealing that the Lhx2 gene is completely inactivated. Cells in mutant HFs also express the anagen-specific gene Shh (arrows) and the S-phase-specific gene His1h3c revealing the presence of proliferating cells (arrows). * indicates melanin deposition. Scale bars 100 um.

Copyright

This image is from Tornqvist G, PLoS Genet 2010;6(4):e1000904, and is displayed under the terms of the Creative Commons Attribution 4.0 International License. J:159209

Associated Alleles

Symbol	Name
Lhx2^tm1.1Lcar	LIM homeobox protein 2; targeted mutation 1.1, Leif Carlsson
Lhx2^tm1Dra	LIM homeobox protein 2; targeted mutation 1, John Drago
Tg(CAG-cre/Esr1*)5Amc	transgene insertion 5, Andrew P McMahon

Associated Genotypes

Allelic Composition	Genetic Background
Lhx2^tm1.1Lcar/Lhx2^tm1Dra Tg(CAG-cre/Esr1*)5Amc/0	involves: 129S4/SvJae * C57BL/6 * CBA