Phenotype Image Detail

Image

Caption

Rspo2^ftls/Rspo2^ftls Rspo3^tm1.1Jcob/Rspo3^tm1.2Jcob Tg(Prrx1-cre)1Cjt/0 double mutants have more severe limb defects than single mutants. Each row shows lateral views of all four limbs from a single newborn animal with the indicated genotype; blue staining is cartilage and red is bone. (a) The wild-type limbs of a control newborn pup with elements labeled for comparison to the other skeletons below: fe, femur; fi, fibula; t, tibia; a, autopod; r, radius; u, ulna; h, humerus; s, scapula; 1, digit 1 (anterior); 5, digit 5 (posterior). (b) Limb skeleton from a Rspo3^tm1.1Jcob/Rspo3^tm1.2Jcob Tg(Prrx1-cre)1Cjt/0 (Prx1-Cre; Rspo3^F/-) mutant. The limb pattern is as in the control, although the stylopodal and zeugopodal elements are slightly shorter. The lines adjacent to these elements represent the lengths of the corresponding segments from the control in (a). (c, d) Limb skeletons from newborn Rspo2^ftls/Rspo2^ftls (Rspo2^Tg/Tg) mutants. (c) This animal had the most severe forelimb phenotype among the 19 Rspo2^ftls/Rspo2^ftls mutants examined. (d) The limbs of this animal showed the most severe hindlimb phenotype among the 19 mice with this genotype. As previously described (Bell et al., 2003) the limb phenotype in these animals is variable with the left hindlimb usually having more severe defects, the most severe of which have a missing autopod, fibula and distal tibia (arrows in (d)). Femora were never malformed. Among 19 animals we scored only two that had severe truncations in both hindlimbs as depicted in (d). Five mice (26%) had a missing left autopod and an intact right autopod. The remaining 12 mice (63%) had substantial autopod elements on both hindlimbs, although usually with missing/malformed digits as indicated by the arrow in (c). These results are similar to those reported for the 77 mice examined in Bell et al., 2003. In Rspo2^ftls/Rspo2^ftls forelimbs the radius is sometimes missing (2 of 19 animals in this study), but more commonly only one or two anterior digits (clear arrowhead) are absent. Posterior digits (including digit 5) are always present. (e-g) Limbs from three Rspo2^ftls/Rspo2^ftls Rspo3^tm1.1Jcob/Rspo3^tm1.2Jcob Tg(Prrx1-cre)1Cjt/0 (Prx1-Cre; Rspo3^F/-; Rspo2^Tg/Tg) double mutant animals. All three show more severe hindlimb defects than the most severe Rspo2^ftls/Rspo2^ftls single mutant (d). The tibia (arrows) are either absent (e) or severely truncated on both sides (f, g). In two animals, the femur is bent and severely shortened (clear arrowhead) on both sides (f, g). In the forelimbs, five of the six limbs are missing digit 5 (arrow) and all are missing digit 1 (clear arrowhead), resulting in a limb with only three shortened middle digits 2-4 (e-g). Both forelimbs in (g) have more proximal defects than the others, including a malformed scapula and humerus. A fourth double-mutant skeleton was stained at E15.5 and showed similar hindlimb truncations and forelimb digit abnormalities as those depicted here. All limbs are shown at the same magnification, scale bar = 1 mm.

Copyright

This image is from Neufeld S, Genesis 2012 Oct;50(10):741-9, and is displayed with the permission of Wiley-Blackwell, who owns the Copyright. J:188812

Associated Alleles

Symbol	Name
Rspo2^ftls	R-spondin 2; footless
Rspo3^tm1.1Jcob	R-spondin 3; targeted mutation 1.1, John Cobb
Rspo3^tm1.2Jcob	R-spondin 3; targeted mutation 1.2, John Cobb
Tg(Prrx1-cre)1Cjt	transgene insertion 1, Clifford J Tabin

Associated Genotypes

Allelic Composition	Genetic Background
Rspo3^tm1.1Jcob/Rspo3^tm1.2Jcob Tg(Prrx1-cre)1Cjt/0	involves: 129S6/SvEvTac * C57BL/6 * CD-1 * SJL
Rspo2^ftls/Rspo2^ftls Rspo3^tm1.1Jcob/Rspo3^tm1.2Jcob Tg(Prrx1-cre)1Cjt/0	involves: 129S6/SvEvTac * C57BL/6 * CD-1 * SJL
Rspo2^ftls/Rspo2^ftls	Not Specified