Phenotypes associated with this allele

• Allele Symbol: Katnb1^{tm1a(EUCOMM)Hmgu}
• Allele Name: targeted mutation 1a, Helmholtz Zentrum Muenchen GmbH
• Allele ID: MGI:4436305
• Summary: 1 genotype

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Katnb1^tm1a(EUCOMM)Hmgu/Katnb1^tm1a(EUCOMM)Hmgu	C57BL/6-Katnb1^tm1a(EUCOMM)Hmgu	MGI:5780454

Genotype
MGI:5780454

hm1

• Allelic Composition: Katnb1^{tm1a(EUCOMM)Hmgu}/Katnb1^{tm1a(EUCOMM)Hmgu}
• Genetic Background: C57BL/6-Katnb1^{tm1a(EUCOMM)Hmgu}
• Cell Lines: HEPD0636_3_F10

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

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:220901 )

• embryos are present in normal Mendelian ratios before E14.5 but are almost never found after E15.5

• some very severely affected embryos die as early as E12.5

embryo

abnormal embryo morphology ( J:220901 )

• all embryos show gross morphological abnormalities with variable phenotypic severity

decreased embryo size ( J:220901 )

• severely reduced body size at E14.5

small limb buds ( J:220901 )

• all embryos show reduced limb bud outgrowth

nervous system

increased brain apoptosis ( J:220901 )

• abundant apoptosis throughout the brain at E12.5, esp. in the proliferative ventricular zones of the cortex, even in mildly affected embryos

abnormal neuronal precursor proliferation ( J:220901 )

• at E12.5, BrdU staining revealed a 35% reduction in the number of actively proliferating cortical progenitors relative to wild-type controls

• striking reduction in cycling ventricular zone progenitors with an even more severe loss of cells that depend upon asymmetrical cell divisions, including intermediate progenitors and neurons

holoprosencephaly ( J:220901 )

• in some embryos

decreased brain size ( J:220901 )

• severe reduction in brain size in some embryos

abnormal forebrain morphology ( J:220901 )

• severe forebrain abnormalities ranging from microcephaly to holoprosencephaly

abnormal cortical ventricular zone morphology ( J:220901 )

• abundant apoptotic cells in the proliferative ventricular zones of the cortex, even in mildly affected embryos, unlike in wild-type controls

loss of cortex neurons ( J:220901 )

• fewer progenitors and post-mitotic neurons present in the cortex at E12.5

thin cerebral cortex ( J:220901 )

• overall cortical thickness is reduced by 54% at E13.5

• however, cell polarity is intact

decreased neuronal precursor cell number ( J:220901 )

• preferential reduction in Tbr2+ intermediate progenitors (72%) and DCX+ neurons (83%) over Sox2+ radial glia (32%) in the cortex at E12.5 relative to wild-type controls

vision/eye

microphthalmia ( J:220901 )

• some embryos are micropthalmic

anophthalmia ( J:220901 )

• some embryos show no eye development

cellular

abnormal cell morphology ( J:220901 )

• 76% of MEFs exhibit supernumerary centrioles; ectopic centrioles show normal 9-fold symmetry but are unpaired, unlike wild-type paired centrioles

• supernumerary centrioles associate with multiple centrosomal proteins with normal stoichiometry, suggesting that they form functional centrosomes

• surprisingly, MEFs exhibit multiple mother centrioles, suggesting additional defects in centriole maturation and identity

abnormal primary cilium morphology ( J:220901 )

• following serum starvation, >35% of MEFs grow supernumerary cilia, nearly 4 times as many as wild-type MEFs

• some MEFs contain only a second, shorter cilium, while others grow 2 or even 3 full-length cilia

• after stimulation by Smoothened agonist (SAG), MEFs fail to show robust relocation of Gli3 and Smoothened (Smo) to the cilium, unlike wild-type MEFs, indicating a deficit in Sonic hedgehog signaling

abnormal cell cytoskeleton morphology ( J:220901 )

• MEFs show changes in cytoskeletal structure with increased acetylated tubulin immunoreactivity around the centrosome, suggesting increased microtubule stability

• MEFs show increased staining for CAMSAP2 (a microtubule minus-end stabilizing protein) and increased linear staining for EB1 (a microtubule plus-end protein), suggesting altered microtubule dynamics

binucleate ( J:220901 )

• binucleate MEFs are observed, likely resulting from aneuploid divisions

aneuploidy ( J:220901 )

• binucleate MEFs are observed, likely resulting from aneuploid divisions

abnormal mitosis ( J:220901 )

• MEFs exhibit misaligned chromosomes

abnormal mitotic spindle morphology ( J:220901 )

• 76% of mutant MEFs contain multipolar mitotic spindles versus 12% in wild-type MEFs

increased brain apoptosis ( J:220901 )

• abundant apoptosis throughout the brain at E12.5, esp. in the proliferative ventricular zones of the cortex, even in mildly affected embryos

decreased fibroblast proliferation ( J:220901 )

• MEFs often fail to proliferate; those that do grow in vitro divide significantly more slowly than wild-type MEFs

abnormal neuronal precursor proliferation ( J:220901 )

• at E12.5, BrdU staining revealed a 35% reduction in the number of actively proliferating cortical progenitors relative to wild-type controls

• striking reduction in cycling ventricular zone progenitors with an even more severe loss of cells that depend upon asymmetrical cell divisions, including intermediate progenitors and neurons

hematopoietic system

abnormal erythropoiesis ( J:220901 )

• lack of red blood cells in the liver, suggesting failed definitive erythropoiesis

limbs/digits/tail

small limb buds ( J:220901 )

• all embryos show reduced limb bud outgrowth

growth/size/body

decreased embryo size ( J:220901 )

• severely reduced body size at E14.5

liver/biliary system

pale liver ( J:220901 )

• all embryos show liver pallor