210) To identify mouse mutants with defects in cortical lamination or corticofugal axon guidance, N-ethyl-N-nitrosourea (ENU) mutagenesis was performed using mice expressing LacZ reporter genes in layers II/III and V of the cortex (Rgs4-lacZ) or in corticofugal axons (TAG1-tau-lacZ). |
PMID:23968836 DOI:10.1093/cercor/bht209 |
2015 Cerebral cortex (New York, N.Y. : 1991) |
* A forward genetic screen in mice identifies mutants with abnormal cortical patterning. |
- Formation of a 6-layered cortical plate and axon tract patterning are key features of cerebral cortex development. Abnormalities of these processes may be the underlying cause for a range of functional disabilities seen in human neurodevelopmental disorders. To identify mouse mutants with defects in cortical lamination or corticofugal axon guidance, N-ethyl-N-nitrosourea (ENU) mutagenesis was performed using mice expressing LacZ reporter genes in layers II/III and V of the cortex (Rgs4-lacZ) or in corticofugal axons (TAG1-tau-lacZ). Four lines with abnormal cortical lamination have been identified. One of these was a splice site mutation in reelin (Reln) that results in a premature stop codon and the truncation of the C-terminal region (CTR) domain of reelin. Interestingly, this novel allele of Reln did not display cerebellar malformation or ataxia, and this is the first report of a Reln mutant without a cerebellar defect. Four lines with abnormal cortical axon development were also identified, one of which was found by whole-genome resequencing to carry a mutation in Lrp2. These findings demonstrated that the application of ENU mutagenesis to mice carrying transgenic reporters marking cortical anatomy is a sensitive and specific method to identify mutations that disrupt patterning of the developing brain. |
(1)101 and | (12)8 including | (23)4 for | (34)2 13 |
(2)36 *null* | (13)7 encoding | (24)4 from | (35)2 but |
(3)28 are | (14)7 involved | (25)4 related | (36)2 can |
(4)26 were | (15)7 which | (26)4 with | (37)2 coding |
(5)25 in | (16)6 (PCGs), | (27)3 had | (38)2 expressed |
(6)16 2 | (17)6 use | (28)3 have | (39)2 is |
(7)14 (13 | (18)5 may | (29)3 stop | (40)2 on |
(8)14 22 | (19)5 that | (30)3 such | (41)2 ranged |
(9)12 start | (20)4 (PCGs) | (31)2 (cytb, | (42)2 to |
(10)11 of | (21)4 as | (32)2 (pnad1 | |
(11)9 was | (22)4 associated | (33)2 (srfAA, |
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