A phenotypic and molecular characterization of the fmr1‐tm1Cgr Fragile X mouse

Genes, Brain and Behavior - Tập 3 Số 6 - Trang 337-359 - 2004
Qijiang Yan1, P. K. Asafo‐Adjei1, H Arnold2, Richard E. Brown3, Robert Bauchwitz1
1Department of Neurology, St. Luke's-Roosevelt Institute for Health Sciences, Columbia University, New York, NY, USA
2Behavioral Neuropharmacology, Sention, Inc., Providence, RI, USA
3Department of Psychology, Dalhousie University, Halifax, Nova Scotia, canada

Tóm tắt

Fragile X Syndrome is the most common form of inherited mental retardation. It is also known for having a substantial behavioral morbidity, including autistic features. In humans, Fragile X Syndrome is almost always caused by inactivation of the X‐linked FMR1 gene. A single knockout mouse model, fmr1‐tm1Cgr, exists. In this report we further characterize the cognitive and behavioral phenotype of the fmr1‐tm1Cgr Fragile X mouse through the use of F1 hybrid mice derived from two inbred strains (FVB/NJ and C57BL/6J). Use of F1 hybrids allows focus on the effects of the fmr1‐tm1Cgr allele with reduced influence from recessive alleles present in the parental inbred strains. We find that the cognitive phenotype of fmr1‐tm1Cgr mice, including measures of working memory and learning set formation that are known to be seriously impacted in humans with Fragile X Syndrome, are essentially normal. Further testing of inbred strains supports this conclusion. Thus, any fmr1‐tm1Cgr cognitive deficit is surprisingly mild or absent. There is, however, clear support presented for a robust audiogenic seizure phenotype in all strains tested, as well as increased entries into the center of an open field. Finally, a molecular examination of the fmr1‐tm1Cgr mouse shows that, contrary to common belief, it is not a molecular null. Implications of this finding for interpretation of the phenotype are discussed.

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Tài liệu tham khảo

10.1126/science.7692601

10.1126/science.1948030

10.1016/S0959-4388(98)80145-1

10.1037/h0077579

Bauchwitz R.P.(1998)Restoration of Natural FMR1 Expression in FMR1 Deficient Mice by P1 Artificial Chromosome Transgenesis.The National Fragile X Foundation San Francisco CA.

10.1093/hmg/9.4.561

Baumgardner T.L., 1995, Specification of the neurobehavioral phenotype in males with fragile X syndrome, Pediatrics, 95, 744, 10.1542/peds.95.5.744

10.1016/0092-8674(91)90514-Y

Bennetto L., 1996, Fragile X Syndrome: Diagnosis, Treatment, and Research., 210

10.1016/S0163-1047(86)90584-4

10.1007/s002130100810

10.1007/BF02212191

10.1023/A:1021694307672

10.1016/S0092-8674(01)00568-2

10.1093/ilar.41.3.163

Bultman S., 2000, Gene Targeting: a Practical Approach., 255

10.2144/97224st01

Butler M.G., 1992, Standards for selected anthropometric measurements in males with the fragile X syndrome, Pediatrics, 89, 1059, 10.1542/peds.89.6.1059

10.1152/jn.1998.79.5.2603

10.1016/S0306-4522(01)00036-7

10.1073/pnas.94.10.5401

Cornish E.C., 1998, Southern hybridization revisited; probe/target DNA interaction is affected by the choice of hybridization buffer, Biotechniques, 25, 948, 10.2144/98256bm04

10.1162/089892901564126

10.1016/S0166-2236(96)20021-9

10.1111/j.1460-9568.1993.tb00927.x

De La Cruz F.F., 1985, Fragile X syndrome, Am J Ment Defic, 90, 119

10.1038/ng0893-335

10.1016/S0306-4522(96)00224-2

10.1016/0031-9384(72)90339-3

10.1016/S0306-4522(00)00292-X

Dutch–Belgian Fragile‐X Consortium, 1994, Fmr1 knockout mice: a model to study fragile X mental retardation, Cell, 78, 23

Dykens E.M., 1987, Strengths and weaknesses in the intellectual functioning of males with fragile X syndrome, Am J Ment Defic, 92, 234

10.1097/00004583-198905000-00021

10.1073/pnas.93.3.1270

10.1016/0166-4328(88)90157-X

Escalante J.A., 1971, Severe sex‐linked mental retardation, J Genet Hum, 19, 137

10.1016/S1097-2765(00)80012-X

10.1136/jnnp.48.2.150

10.1002/(SICI)1096-8628(19990402)83:4<257::AID-AJMG5>3.0.CO;2-U

10.1002/(SICI)1096-8628(19990528)84:3<277::AID-AJMG22>3.0.CO;2-W

10.1038/nn834

10.1093/schbul/13.4.669

10.1037/0735-7044.107.4.618

10.1016/S0166-2236(96)20020-7

10.1093/schbul/13.4.643

10.1002/(SICI)1096-8628(19960809)64:2<246::AID-AJMG2>3.0.CO;2-S

Goelz M.F., 1998, Neuropathologic findings associated with seizures in FVB mice, Laboratory Anim Sci, 48, 34

10.1073/pnas.141145998

Hagerman R.J., 1996, Fragile X Syndrome: Diagnosis, Treatment, and Research, 210

10.1002/jemt.10067

10.1007/BF00504983

Hodapp R.M., 1992, K‐ABC profiles in children with fragile X syndrome, Down syndrome, and nonspecific mental retardation, Am J Ment Retard, 97, 39

10.1016/0926-6410(96)00004-3

10.1073/pnas.122205699

Jerison H.J., 1973, Evolution of the Brain and Intelligence

10.1016/S0378-5955(97)00155-X

Katz E. Rothschild O. Herrera A. Huang S. Wong A. Wojciechowski Y. Gil A. Yan Q.&Bauchwitz R.(2003)Murine odor based behavioral tasks confounded by distance dependent detection: modfication of a digging paradigm.Cogprints(cogprints.ecs.soton.ac.uk/archive/00003316).

10.1002/(SICI)1096-8628(19990402)83:4<286::AID-AJMG10>3.0.CO;2-H

10.1002/ajmg.1320300118

10.1093/hmg/4.5.783

10.1016/S0301-0082(98)00098-7

10.1037/h0036970

10.1002/(SICI)1096-8628(19960809)64:2<241::AID-AJMG1>3.0.CO;2-X

10.1093/hmg/10.4.329

10.1016/S0166-2236(96)20022-0

10.1006/mcne.2001.1085

10.1093/nar/29.11.2276

10.1007/BF00177912

10.1136/jnnp.6.3-4.154

10.1111/j.1469-8749.1999.tb00664.x

10.1016/S0006-8993(00)02617-2

10.1002/(SICI)1096-8628(19990402)83:4<268::AID-AJMG7>3.0.CO;2-K

10.1002/hipo.10005

10.1016/S0896-6273(03)00034-5

10.1016/S0092-8674(00)81972-8

10.1136/jmg.34.1.1

10.1006/brcg.1999.1200

10.1016/S0028-3932(00)00036-1

10.1111/j.1528-1157.2000.tb01499.x

10.1111/j.1528-1157.1999.tb00824.x

10.1016/S0006-8993(01)03309-1

10.1523/JNEUROSCI.21-14-05139.2001

10.1016/S0168-9525(01)02619-1

10.1046/j.1365-2788.2000.00279.x

10.1016/0031-9384(87)90286-1

10.1016/S0306-4522(99)00285-7

10.1007/s002130050333

10.1037/0735-7044.110.6.1415

10.1093/hmg/9.8.1145

10.1016/0091-3057(86)90552-6

10.1073/pnas.88.19.8322

10.1034/j.1601-183X.2002.10205.x

10.1016/S0165-0270(98)00169-1

10.1016/S0166-4328(96)00164-7

Rogers L.J., 1998, Minds of Their Own: Thinking and Awareness in Animals,

10.1097/00001756-200108080-00056

10.1111/j.2044-8295.1973.tb01369.x

10.1016/0306-4522(90)90139-U

10.1007/BF02244990

10.1016/0092-8674(93)90420-U

Strupp B.J., 1990, An animal model of retarded cognitive development, Adv Infancy Res, 6, 149

10.1093/hmg/1.6.397

10.1083/jcb.137.7.1615

10.1007/BF02244948

10.1002/(SICI)1096-8628(19960712)64:1<196::AID-AJMG35>3.0.CO;2-G

10.1016/S0169-328X(99)00310-1

10.1016/S0166-4328(00)00296-5

10.1037/0033-2909.83.3.482

10.1002/(SICI)1096-8628(19990402)83:4<248::AID-AJMG3>3.0.CO;2-1

10.1016/S0028-3932(01)00212-3

10.1016/S0378-5955(00)00137-4

Wolfer D.P., 1998, Spatial memory and learning in transgenic mice: fact or artifact?, News Physiol Sci, 13, 118

Zachmann M., 1974, Testicular volume during adolescence. Cross‐sectional and longitudinal studies, Helv Paediatr Acta, 29, 61

10.1016/S0092-8674(03)00079-5

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Genes, Brain and Behavior

Tập 3 Số 6

337-359

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