B6;129T-Dnah11^iv/J

Stock number: 000773
Product name: situs inversus viscerum
Research areas: Developmental Biology Research

Description

These mice carry a spontaneous mutation at the Dnah11 locus characterized by inverse placement of the visceral and thoracic organs and in anomalous positioning and interactions of blood vessels. They are suitable for use in applications related to the study of abnormal laterality in humans.

Detailed description

DNAH11 is important for developmental control of organ positioning in the left-right axis such that homozygosity for the situs inversus viscerum (iv) mutant allele can result not only in inverse placement of the visceral and thoracic organs, but also in anomalous positioning and interactions of blood vessels (including the hepatic portal, inferior vena cava, and azygos vein) and modified shape of organs and blood vessels, including abnormal lobation of lungs or liver. Approximately 50% of mice homozygous for Dnah11^iv have situs inversus, and the likelihood of situs inversus is not impacted by whether the homozygous parent has situs inversus. This indicates that wild type Dnah11 instructs left-right asymmetry, and in the absence of functional Dnah11 the direction of this asymmetry is random. Heterotaxia is found in less than half of homozygotes and occurs equally in those that do and do not have situs inversus. While heterotaxia may be impacted by genetic background, the incidence of situs inversus has not shown this variation. Situs inversus can be identified shortly after birth, until the skin thickens at approximately day 5, by viewing the location of the milk-filled stomach through the skin. Homozygotes are generally viable and do breed, although poorreproductive performance with a high rate of resorption has been reported by Brown et al. (Development 1989). Some premature death has been reported and may be caused by deformities of the cardiac loop. (Hummel and Chapman, 1959; Layton 1976; Brown et al., 1989; Icardo and Colvee, 2001.)

Development

In 1956 Katherine Hummel reported finding situs inversus viscerum (iv) in 6 out of 42 mice in the F3 generation from a cross of a C3H/e female with an my/my male. This my/my male was likely from the line that was then being inbred to become My/Hu (see stock#000265). The my mutation was bred out of this new mutant stock and in 1972 the iv-bearing stock was transferred from Katherine Hummel to Robert Collins, both at The Jackson Laboratory. Collins began inbreeding from the outbred stock in 1975 and this generated the strain SI/Col (see stock#001045) which is homozygous for Dnah11^iv, a, and Tyrp1^b. SI/Col reached F62 in 1994. At some point the Dnah11^iv mutation was bred onto 129/Sv-ter but the details of this breeding have been lost. In 1981 males homozygous for Dnah11^iv on the 129/Sv-ter background were bred to C57BL/6J females to generate embryos for cryopreservation.

Allele

Symbol: Dnah11^iv
Name: situs inversus viscerum
MGI accession ID: MGI:1856917
Generation method: Spontaneous
Marker symbol: Dnah11
Marker name: dynein, axonemal, heavy chain 11
Chromosome: 12
Strain of origin: (C3HeB/Fe x STOCK Frem2^my)F3
Molecular note: A G-to-A transition mutation led to a substitution of glutamate with lysine at position 2271 (p.E2271K)in the encoded protein. This residue is located between the second and third P-loop motifs, a highly conserved region that constitutes the motor domain.