STOCK T^c/J

Stock number: 001814
Product name: curtailed
Research areas: Developmental Biology Research, Neurobiology Research

Description

The curtailed mutation is one of the most severe heterozygous-viable alleles of brachyury.

Detailed description

Mice heterozygous for the semidominant curtailed allele of brachyury usually have only a short, boneless caudal filament in place of the tail, although a few have short tails. Some heterozygotes die between birth and weaning. Low-grade spina bifida and blood blisters just dorsal of the caudal filament, occasional hind-limb paralysis, or atresia ani have also been observed (Searle, 1965). Heterozygotes lack the odontoid process of the axis and intervertebral nuclei pulposi, except for traces in the lower thoracic and lumbar regions. There are wider than normal cervical vertebral centra and the atlas has an abnormal shape in the ventral arch. Missing and fused vertebrae, and fused and malformed ribs are also standard phenotypes. Ventral duplication of the neural tube or spinal cord also occur in heterozygotes.

Curtailed homozygotes die between embryonic day 9.5 and 10.5 with failed placental connections. They lack the posterior part of the body to a greater degree than do brachyury (T) homozygotes. Truncation of the primitive streak diminishes its insertion into the exocoelom, no allantoic core domain is then found in the allantois, and the anterior position of the allantoic-yolk sac junction results in placement within the embryonic compartment rather than extraembryonic. As a result, medial umbilical roots are foreshortened in homozygotes disrupting the organization of the vessel of confluence and umbilical artery (Rodriquez et al., 2017). T^c is dominant to T^h but not to T. T^c/t^h7 compound heterozygotes have a tail that is shorter than normal, but present.

Development

A C3H/HeH female bred with a 101/H male was irradiated when 17 days pregnant and the offspring were mated with T stock, which was a non-inbred testing stock homozygous for seven recessive alleles, a, Tyrp1^b, Tyr^c-ch, Oca2^p, Myo5a^d, Bmp5^se, and Ednrb^s. One female offspring had a very short caudal filament instead of a normal tail and she was bred to an unrelated (C3H/HeH x 101/H)F1 male and produced nearly 50% offspring with the T^c phenotype. At some point a cross was done that introduced the tufted mutation (Itpr3^tf) into the line from an undefined source. In 1991 some mice that were black agouti and carrying T^c and Itpr3^tf were shipped from the laboratory of Dr. Dorothea Bennett at The University of Texas, Austin, to The Mouse Mutant Resource at The Jackson Laboratory. These were sibling intercrossed for three generations and embryos were generated for cryopreservation from C3H/HeSnJ females bred with males carrying T^c and undefined for Itpr3^tf. 15 years later IFV generated cryopreserved embryos from cryo-recovered T^c males and C3H/HeSnJ females.

Allele

Symbol: T^c
Name: curtailed
MGI accession ID: MGI:1856185
Generation method: Radiation induced
Marker symbol: T
Marker name: brachyury, T-box transcription factor T
Chromosome: 17
Strain of origin: (C3H/HeH x 101/H)F1
Molecular note: Southern analysis of genomic DNA showed that this allele does not comprise a deletion of flanking loci, D17Leh119II and D17RP17, as found for alleles T^hp and T^Orl. Sequencing genomic DNA from the open reading frame revealed a 19 bp deletion of GCACACGGTCTCAGCTGCC predicted to result in a protein truncated at the carboxyl-terminal end.
General note: T^c, curtailed, semidominant. Found among offspring from a cross between a multiple recessive testing stock, T stock, and a pup from an irradiated C3H/HeH female that had been impregnated by a 101/H male. Heterozygotes have complete or near-complete absence of the tail, absence of the odontoid process of the axis, absence of the nucleus pulposi of the intervertebral discs, a tendency for rib and vertebral fusions, and a slight decrease in average number of presacral vertebrae. They occasionally show paralysis of the hindlimbs and atresia ani. Homozygotes die at the same time as T/T embryos and are similar to them but more severely affected. T^c/T embryos are variable and intermediate between T/T and T ^c/T ^c (J:5003).