Mouse Genome Informatics
hm1
    Acvr2btm1Enl/Acvr2btm1Enl
either: (involves: 129S4/SvJae) or (involves: 129S4/SvJae * C57BL/6J)
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• Background Sensitivity: on the 129S4 background, no homozygotes are seen at weaning
• on a mixed 129S4 and C57BL/6 background, 30% survive past weaning and these are viable and fertile

cardiovascular system
• abnormal looping of the descending aorta on a 129S4 background, with 51% showing looping toward the right instead of the left as in wild-type
• Background Sensitivity: all mice on the 129S4 background and 60% on the mixed 129S4 and C57BL/6 background exhibit defects in the patterning of the outflow tract
• the two great arteries are located in abnormal positions
• the aorta arises from the anterior-most position of the heart and the pulmonary trunk is located posterior to and on either the left or right side of the aorta
• the pulmonary trunk and the aorta are in parallel positions without crossing over each other
• on the 129S4 background, the apex of the heart points in a random direction instead of to the left
• some mutants show left superior vena cava connected to the left atrium
• 30% of homozygotes on the 129S4 background show right atrial isomerism
• Background Sensitivity: seen in 30% of mice on a 129S4 background and a lower frequency in mice on the mixed 129S4 and C57BL/6 background
• Background Sensitivity: seen in 30% of mice on a 129S4 background

hematopoietic system
• abnormally shaped spleen

homeostasis/metabolism

renal/urinary system
• Background Sensitivity: 80% and 53% of homozygotes on the 129S4 and the mixed 129S4 and C57BL/6 backgrounds, respectively, show renal hypoplasia
• exhibit a spectrum of renal abnormalities including uni- or bilateral agenesis
• exhibit a spectrum of renal abnormalities including uni- or bilateral agenesis

respiratory system
• Background Sensitivity: 100% of homozygotes exhibit right pulmonary isomerism (RPI) and cardiac malformations on the 129S4 background, while on the mixed 129S4 and C57BL/6 background, all homozygotes with outflow tract defects show RPI, whereas all viable mice have normal hearts and lungs
• the left lung has four lobes, in mirror image to the right lung
• morphology and branching patterns of the bronchi appear to be bilaterally symmetric, and in most cases, both bronchi are eparterial

skeleton
• have 9 vertebrosternal ribs and 7 free ribs
• frequently the first rib (T1) on vertebra 8 (V8) is fused to the second rib (T2) on the ventral side and connected to the sternum at the T2 position
• have 16, instead of 13, thoracic vertebrae, displaying the C7/T16/L6 vertebral configuration
• shape of the dorsal side of V9 (T2) vertebra is similar to that of V8 (T1) of wild-type
• the largest spinous process, a characteristic of V9 (T2) vertebra, is present at V10 (T3)
• the transition of the spinous process shape occurs at V18 and V20, instead of at V16 and V17, as in wild-type
• spinous process of V19 pints in the posterior direction although its shape looks similar to V17
• last pair of thoracic ribs are attached to V23 instead of V20

liver/biliary system
• although the liver has the same number and patterns of lobes as wild-type, the shape of some lobes is slightly altered

growth/size/body
• some mutants show left superior vena cava connected to the left atrium
• 30% of homozygotes on the 129S4 background show right atrial isomerism
• Background Sensitivity: 100% of homozygotes exhibit right pulmonary isomerism (RPI) and cardiac malformations on the 129S4 background, while on the mixed 129S4 and C57BL/6 background, all homozygotes with outflow tract defects show RPI, whereas all viable mice have normal hearts and lungs
• the left lung has four lobes, in mirror image to the right lung

immune system
• abnormally shaped spleen


Mouse Genome Informatics
hm2
    Acvr2btm1Enl/Acvr2btm1Enl
involves: 129S4/SvJae
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
skeleton
• exhibit a series of homeotic transformations of vertebrae, which results in an increase of three thoracic vertebrae and of two vertebrosternal ribs
• the 23rd vertebra was transformed to the 16th thoracic vertebra instead of the 3rd lumbar vertebra as in wild-type
• vertebra 29 was transformed to the 6th lumbar vertebra instead of to the 3rd sacral vertebra as in wild-type

embryogenesis
• 21 of 31 show effects associated with left-right asymmetry such as right pulmonary isomerism and transposition of great arteries

cardiovascular system

growth/size/body

respiratory system


Mouse Genome Informatics
cx3
    Acvr2atm1Hsch/Acvr2atm1Hsch
Acvr2btm1Enl/Acvr2btm1Enl

involves: 129S1/Sv * 129S4/SvJae * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• die before or during gastrulation and are resorbed by E8.5

embryogenesis
• cell death is seen in the epiblast of some embryos
• do not form mesoderm
• exhibit a constriction at the embryonic and extraembryonic junction and the separation of the visceral endoderm and the epiblast
• embryos are growth arrested at the early egg cylinder stage

cellular
• cell death is seen in the epiblast of some embryos


Mouse Genome Informatics
cx4
    Acvr2atm1Hsch/Acvr2atm1Hsch
Acvr2btm1Enl/Acvr2b+

involves: 129S1/Sv * 129S4/SvJae * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• die before or during gastrulation; by E9.5, embryos are partially or completely degenerated

embryogenesis
• gastrulation is initiated but severely impaired subsequently
• severe gastrulation defects ranging from the lack of discernible embryonic axes to the formation or relatively normal axial and paraxial structures
• primitive streak elongation is disrupted
• formation of the embryonic mesoderm is severely impaired
• exhibit defects in anterior patterning as indicated by marker expression
• the few embryos that are able to undergo relatively normal gastrulation, exhibit abnormal anterior neural development
• almost all embryos with gastrulation defects do not form the head-fold structure
• often show a constriction at the embryonic and extraembryonic junction, leading to the protrusion of embryos outside the yolk sac at E8.5
• absent in most mutants
• absent in most mutants

cardiovascular system
• almost all embryos with gastrulation defects do not form a primitive heart


Mouse Genome Informatics
cx5
    Acvr2atm1Hsch/Acvr2a+
Acvr2btm1Enl/Acvr2btm1Enl

involves: 129S1/Sv * 129S4/SvJae * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• die late in development or shortly after birth