A genetic study of the suppressors of the Engrailed-1 cerebellar phenotype
Abstract The mouse Engrailed genes, En1 and En2 , play an important role in the development of the cerebellum from its inception at the mid/hindbrain boundary in early embryonic development through cell type specification events and beyond. In the absence of En1 , the cerebellum and caudal midbrain...
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| Published in: | Brain research Vol. 1140; pp. 170 - 178 |
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06-04-2007
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| Abstract | Abstract The mouse Engrailed genes, En1 and En2 , play an important role in the development of the cerebellum from its inception at the mid/hindbrain boundary in early embryonic development through cell type specification events and beyond. In the absence of En1 , the cerebellum and caudal midbrain fail to develop normally—a phenotype that we have previously reported to be strain dependent. On the 129/S1 strain background, En1 null alleles lead to mid/hindbrain failure, whereas on the C57BL/6 background, En1 deficiency is compatible with near normal cerebellar development. We have pursued this dramatic effect of genetic background by performing a genetic modifier screen through F1 backcross and F1 intercross matings. The backcross has yielded two strong candidate intervals with suggestive linkage to a third region. Moreover, variations in rescue frequency among subgroups within the backcross indicate gender and parent of origin influences on rescue penetrance. The intercross data reveal locus heterogeneity of the En1 modifiers, with more than one compliment of C57BL/6 and 129/S1 alleles capable of mediating the rescue phenotype. These findings highlight the complexity and plasticity of gene networks involved in brain development. |
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| AbstractList | The mouse Engrailed genes, En1 and En2, play an important role in the development of the cerebellum from its inception at the mid/hindbrain boundary in early embryonic development through cell type specification events and beyond. In the absence of En1, the cerebellum and caudal midbrain fail to develop normally--a phenotype that we have previously reported to be strain dependent. On the 129/S1 strain background, En1 null alleles lead to mid/hindbrain failure, whereas on the C57BL/6 background, En1 deficiency is compatible with near normal cerebellar development. We have pursued this dramatic effect of genetic background by performing a genetic modifier screen through F1 backcross and F1 intercross matings. The backcross has yielded two strong candidate intervals with suggestive linkage to a third region. Moreover, variations in rescue frequency among subgroups within the backcross indicate gender and parent of origin influences on rescue penetrance. The intercross data reveal locus heterogeneity of the En1 modifiers, with more than one compliment of C57BL/6 and 129/S1 alleles capable of mediating the rescue phenotype. These findings highlight the complexity and plasticity of gene networks involved in brain development. The mouse Engrailed genes, En1 and En2, play an important role in the development of the cerebellum from its inception at the mid/hindbrain boundary in early embryonic development through cell type specification events and beyond. In the absence of En1, the cerebellum and caudal midbrain fail to develop normally—a phenotype that we have previously reported to be strain dependent. On the 129/S1 strain background, En1 null alleles lead to mid/hindbrain failure, whereas on the C57BL/6 background, En1 deficiency is compatible with near normal cerebellar development. We have pursued this dramatic effect of genetic background by performing a genetic modifier screen through F1 backcross and F1 intercross matings. The backcross has yielded two strong candidate intervals with suggestive linkage to a third region. Moreover, variations in rescue frequency among subgroups within the backcross indicate gender and parent of origin influences on rescue penetrance. The intercross data reveal locus heterogeneity of the En1 modifiers, with more than one compliment of C57BL/6 and 129/S1 alleles capable of mediating the rescue phenotype. These findings highlight the complexity and plasticity of gene networks involved in brain development. Abstract The mouse Engrailed genes, En1 and En2 , play an important role in the development of the cerebellum from its inception at the mid/hindbrain boundary in early embryonic development through cell type specification events and beyond. In the absence of En1 , the cerebellum and caudal midbrain fail to develop normally—a phenotype that we have previously reported to be strain dependent. On the 129/S1 strain background, En1 null alleles lead to mid/hindbrain failure, whereas on the C57BL/6 background, En1 deficiency is compatible with near normal cerebellar development. We have pursued this dramatic effect of genetic background by performing a genetic modifier screen through F1 backcross and F1 intercross matings. The backcross has yielded two strong candidate intervals with suggestive linkage to a third region. Moreover, variations in rescue frequency among subgroups within the backcross indicate gender and parent of origin influences on rescue penetrance. The intercross data reveal locus heterogeneity of the En1 modifiers, with more than one compliment of C57BL/6 and 129/S1 alleles capable of mediating the rescue phenotype. These findings highlight the complexity and plasticity of gene networks involved in brain development. |
| Author | Murcia, Crystal L Cherosky, Natalie A Herrup, Karl Gulden, Forrest O |
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| CitedBy_id | crossref_primary_10_1038_srep31701 crossref_primary_10_1016_j_tice_2022_101897 crossref_primary_10_1016_j_neuroscience_2007_06_012 crossref_primary_10_1113_JP280978 crossref_primary_10_3389_fnagi_2024_1337365 crossref_primary_10_1007_s00429_012_0482_6 crossref_primary_10_4015_S1016237216500277 |
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| Keywords | En2 En1 Genetic background Modifier gene Cerebellum development Cerebellum Rodentia Central nervous system Genetic determinism Encephalon Neurological mutation Vertebrata Phenotype Mammalia Gene Mouse Animal Development Genetics En1;En2;Cerebellum development;Genetic background;Modifier gene |
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| Snippet | Abstract The mouse Engrailed genes, En1 and En2 , play an important role in the development of the cerebellum from its inception at the mid/hindbrain boundary... The mouse Engrailed genes, En1 and En2, play an important role in the development of the cerebellum from its inception at the mid/hindbrain boundary in early... The mouse Engrailed genes, En1 and En2, play an important role in the development of the cerebellum from its inception at the mid/hindbrain boundary in early... The mouse Engrailed genes, En1 and En2, play an important role in the development of the cerebellum from its inception at the mid /hindbrain boundary in early... |
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| SourceType | Aggregation Database Index Database Publisher |
| StartPage | 170 |
| SubjectTerms | Animals Biological and medical sciences Cerebellum - embryology Cerebellum - metabolism Cerebellum development Chromosome Mapping - methods Development. Senescence. Regeneration. Transplantation En1 En2 Female Fundamental and applied biological sciences. Psychology Gene Expression Regulation, Developmental Gene Regulatory Networks Genetic background Homeodomain Proteins - genetics Homeodomain Proteins - metabolism Lod Score Mice Mice, Inbred C57BL Mice, Knockout Modifier gene Nerve Tissue Proteins - genetics Nerve Tissue Proteins - metabolism Neurology Phenotype Pregnancy Rhombencephalon - embryology Rhombencephalon - metabolism Vertebrates: nervous system and sense organs |
| Title | A genetic study of the suppressors of the Engrailed-1 cerebellar phenotype |
| URI | https://www.clinicalkey.es/playcontent/1-s2.0-S0006899306018841 https://dx.doi.org/10.1016/j.brainres.2006.06.076 https://www.ncbi.nlm.nih.gov/pubmed/16884697 https://search.proquest.com/docview/19662992 https://search.proquest.com/docview/70255460 |
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