The phenotypic characteristics of heterozygous reeler mouse

Abstract

Histological and behavioral traits are associated with reelin (Reln) haplo-insufficiency in heterozygous reeler mouse (rl+/-). These phenotypic traits are an approximately 50% decrease of brain Reln mRNA and Reln protein, an accumulation of nicotinamide-adenine dinucleotide phosphate-diaphorase (NADPH-d)-positive neurons in subcortical white matter, an age-dependent decrease in prepulse inhibition of startle (PPI), and neophobic behavior on the elevated plus-maze. Possible analogies between these rl+/- phenotypic traits and signs of psychosis vulnerability are discussed.

Reelin glycoprotein: structure, biology and roles in health and disease

“…However, the latter investigators used a scoring technique which was semiquantitative and had a smaller N for each patient population. 7 This disparity in levels of Reelin protein production appears similar to the scenario seen in Reeler homozygous mutant mice 2 (with no Reelin production) versus Reeler heterozygous mutation 40 and that seen following prenatal viral infection 18 where brain Reelin levels are reduced by 50%. Thus, a similar mechanism may be operational in various neuropsychiatric disorders where Reelin production may be affected selectively by various mutations or selective hypermethylation of the Reln promoter, 64,65 causing either profound (schizophrenia, autism, lissencephaly) or moderate (bipolar, depressed) cognitive deficits 50,52,77,59 associated with their respective Reelin levels.…”

“…More interestingly, several experimental paradigms and haploinsufficiency in Reln gene in mice also cause decreases in Reelin production with resultant cortical and behavioral abnormalities. 18,[39][40][41] In the heterozygous reeler mutation, there is a 50% reduction in Reelin protein and mRNA, decrease in dendritic spine density in frontal cortex, neuropil hypoplasticity, decreased GAD67 expression and decreased GABA turnover. 42 Additionally, the heterozygous reeler mutant mice exhibit decreased prepulse inhibition, 40 a phenomenon observed in schizophrenia and autism.…”

“…18,[39][40][41] In the heterozygous reeler mutation, there is a 50% reduction in Reelin protein and mRNA, decrease in dendritic spine density in frontal cortex, neuropil hypoplasticity, decreased GAD67 expression and decreased GABA turnover. 42 Additionally, the heterozygous reeler mutant mice exhibit decreased prepulse inhibition, 40 a phenomenon observed in schizophrenia and autism. 43,44 Prenatal human influenza viral infection in midterm pregnant mice leads to abnormal corticogenesis, 18 decrease in brain Reelin protein content 18 and reduced prepulse inhibition.…”

“…57 Moreover, mice that lack the Reelin receptors ApoER2 or VLDL-R have pronounced defects in memory formation and LTP. 57 Other behavioral and biochemical data also show that reductions in levels of Reelin in brain or blood, following postnatal hypoxia, 58 prenatal viral infection in midgestation 18,45 and in heterozygous reeler mutants 40 cause abnormalities in behavior such as decrease in prepulse inhibition (PPI), increase in anxiety and decrease in memory formation. Additionally, mutations in RELN gene have been associated with significant learning disability, hypoplastic cerebellum, ataxia and cognitive decline in man and mouse.…”

Advances in behavioral genetics: mouse models of autism

“…162,163 Reln rl/ þ mice, which retain approximately 50% of normal Reln expression, do not show the reeling gait characteristic of the Reln rl/rl animals. There are variable reports of an abnormal behavioral phenotype in Reln rl/ þ mice, including findings of selective impairments in reversal learning, 164 increased anxiety-like behavior, decreases in prepulse inhibition of acoustic startle responses, 165 deficits in odor discrimination 166 and impaired contextual fear conditioning. 167 However, other researchers have found normal reversal learning, contextual fear conditioning and working memory, 168 and unchanged sensorimotor gating, social responses and other indexes of cognitive function 157,169 in heterozygous mice.…”