Phenotypes associated with this allele

• Allele Symbol: Dchs1^tm1.2Irv
• Allele Name: targeted mutation 1.2, Kenneth Irvine
• Allele ID: MGI:4867020
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Dchs1^tm1.2Irv/Dchs1^tm1.2Irv	involves: 129S7/SvEvBrd * C57BL/6	MGI:5695321
hm2	Dchs1^tm1.2Irv/Dchs1^tm1.2Irv	involves: 129S/Sv * C57BL/6 * CBA	MGI:4941821
ht3	Dchs1^tm1.2Irv/Dchs1^+	involves: 129S7/SvEvBrd * C57BL/6	MGI:5695318
cx4	Dchs1^tm1.2Irv/Dchs1^tm1.2Irv Fat4^tm1.1Hmc/Fat4^tm1.1Hmc	involves: 129 * C57BL/6 * CBA	MGI:4941823

Genotype
MGI:5695321

hm1

• Allelic Composition: Dchs1^tm1.2Irv/Dchs1^tm1.2Irv
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

cardiovascular system

abnormal mitral valve morphology ( J:225789 )

• severe mitral-valve shape changes are seen at E15.5-E17.5, with changes in valve length and width at E17.5

Genotype
MGI:4941821

hm2

• Allelic Composition: Dchs1^tm1.2Irv/Dchs1^tm1.2Irv
• Genetic Background: involves: 129S/Sv * C57BL/6 * CBA

mortality/aging

perinatal lethality, complete penetrance ( J:169135 )

postnatal lethality, complete penetrance ( J:169135 )

• if wild-type littermates are removed some mice can survive for a couple of weeks

growth/size/body

kidney cyst ( J:169135 )

• apparent decrease in the number and size of cysts compared to Fat4 homozygous null mice

postnatal growth retardation ( J:169135 )

• fail to grow, remaining the similar in size to newborn pups, but do show some signs of postnatal development

hearing/vestibular/ear

abnormal cochlea morphology ( J:169135 )

• about 20% shorter than in wild-type controls

abnormal orientation of cochlear hair cell stereociliary bundles ( J:169135 )

• subtle (less than 2 degrees) differences in the average orientation of stereocilia

nervous system

abnormal neural tube morphology ( J:169135 )

• modest increase in the width to height ratio

abnormal orientation of cochlear hair cell stereociliary bundles ( J:169135 )

• subtle (less than 2 degrees) differences in the average orientation of stereocilia

renal/urinary system

kidney cyst ( J:169135 )

• apparent decrease in the number and size of cysts compared to Fat4 homozygous null mice

abnormal kidney collecting duct morphology ( J:169135 )

• at E15.5 a modest but significant increase in the number of cells around the circumference of distal collecting ducts is detected

dilated kidney collecting duct ( J:169135 )

• slightly dilated at P0

abnormal kidney development ( J:169135 )

• striking clusters of apoptotic cells are detected in the epithelium and mesenchyme as early as E11.5

small kidney ( J:169135 )

• difference in size is first detectable at E11.5 and the difference increases until E13.5 then remains fairly consistent from E15.5 to P0

abnormal renal tubule morphology ( J:169135 )

• slightly less straight at P0

dilated renal tubule ( J:169135 )

• slightly dilated at P0

impaired branching involved in ureteric bud morphogenesis ( J:169135 )

• by E11.5 branching of the ureteric epithelium in mutants lags behind that of wild-type littermates

• by 12.5 kidney growth and branching are substantially decreased and the ureteric epithelium is wider and more irregular than in wild-type littermates

skeleton

short sternum ( J:169135 )

• shorter than normal

wide sternum ( J:169135 )

• wider than normal

abnormal spine curvature ( J:169135 )

• often have a bent spine

abnormal vertebrae morphology ( J:169135 )

abnormal thoracic vertebrae morphology ( J:169135 )

• vertebrae in the lumbar and posterior thoracic regions show a modest increase in the width and are narrower along the anterior-posterior axis

• the centrum at the midline is malformed

abnormal lumbar vertebrae morphology ( J:169135 )

• vertebrae in the lumbar and posterior thoracic regions show a modest increase in the width and are narrower along the anterior-posterior axis

• the centrum at the midline is malformed

abnormal vertebrae development ( J:169135 )

• dual ossification centers are present in vertebrae in the lumbar and posterior thoracic regions

abnormal endochondral bone ossification ( J:169135 )

• dual ossification centers are present in vertebrae in the lumbar and posterior thoracic regions

abnormal sternum ossification ( J:169135 )

• abnormal ossification pattern

limbs/digits/tail

curly tail ( J:169135 )

• often seen

cardiovascular system

abnormal interatrial septum morphology ( J:169135 )

• the septum primum is often thinner and the ostium secundum is much larger than in wild-type littermates

digestive/alimentary system

abnormal intestine morphology ( J:169135 )

• on average total intestinal length is about 72% that of wild-type littermates

respiratory system

small lung ( J:169135 )

embryo

abnormal neural tube morphology ( J:169135 )

• modest increase in the width to height ratio

Genotype
MGI:5695318

ht3

• Allelic Composition: Dchs1^tm1.2Irv/Dchs1⁺
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6

cardiovascular system

abnormal mitral valve morphology ( J:225789 )

• changes in mitral-valve shape are seen at E15.5-E17.5, but not at E11.5-E13.5, with changes in valve length and width at E17.

abnormal mitral valve cusp morphology ( J:225789 )

• myxomatous degeneration with increased proteoglycan accumulation in both mitral leaflets

thick mitral valve cusps ( J:225789 )

• prominent posterior leaflet thickening with increases in valve volume in adults

mitral valve prolapse ( J:225789 )

• mitral valve prolapse with pronounced involvement of the posterior leaflet, which is elongated and shifts the leaflet coaptation anteriorly

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
mitral valve prolapse		DOID:988	OMIM:157700 OMIM:607829 OMIM:610840	J:225789

Genotype
MGI:4941823

cx4

• Allelic Composition: Dchs1^tm1.2Irv/Dchs1^tm1.2Irv; Fat4^tm1.1Hmc/Fat4^tm1.1Hmc
• Genetic Background: involves: 129 * C57BL/6 * CBA

hearing/vestibular/ear

abnormal orientation of cochlear hair cell stereociliary bundles ( J:169135 )

• mostly subtle (less than 2 degrees) differences in the average orientation of stereocilia

abnormal orientation of outer hair cell stereociliary bundles ( J:169135 )

• in the outermost row of hair cells there is a 4 degree difference in the average orientation of stereocilia

nervous system

abnormal neural tube morphology ( J:169135 )

• increase in the width to height ratio

abnormal orientation of cochlear hair cell stereociliary bundles ( J:169135 )

• mostly subtle (less than 2 degrees) differences in the average orientation of stereocilia

abnormal orientation of outer hair cell stereociliary bundles ( J:169135 )

• in the outermost row of hair cells there is a 4 degree difference in the average orientation of stereocilia

skeleton

short sternum ( J:169135 )

• shorter than normal

wide sternum ( J:169135 )

• wider than normal

abnormal thoracic vertebrae morphology ( J:169135 )

• vertebrae in the lumbar and posterior thoracic regions show a modest increase in the width and are narrower along the anterior-posterior axis

• the centrum at the midline is malformed

abnormal vertebrae development ( J:169135 )

• dual ossification centers are present in vertebrae in the lumbar and posterior thoracic regions

abnormal endochondral bone ossification ( J:169135 )

• dual ossification centers are present in vertebrae in the lumbar and posterior thoracic regions

abnormal sternum ossification ( J:169135 )

• abnormal ossification pattern

respiratory system

small lung ( J:169135 )

embryo

abnormal neural tube morphology ( J:169135 )

• increase in the width to height ratio